Molecularly imprinted polymeric coatings for sensitive and selective gravimetric detection of artemether

Monitoring antimalarial drugs is necessary for clinical assays, human health, and routine quality control practices in pharmaceutical industries. Herein, we present the development of sensor coatings based on molecularly imprinted polymers (MIPs) combined with quartz crystal microbalance (QCM) for sensitive and selective gravimetric detection of an antimalarial drug: artemether. The MIP coatings are synthesized by using artemether as the template in a poly(methacrylic acid-co-ethylene glycol dimethacrylate) matrix. Artemether-MIP and the non-imprinted polymer (NIP) control or reference layers are deposited on 10 MHz dual-electrode QCM by spin coating (187 ± 9 nm layer thickness after optimization). The coatings are characterized by FTIR spectroscopy and atomic force microscopy that reveal marked differences among the MIP and NIP. The MIP-QCM sensor exhibits high sensitivity (0.51 Hz ppm⁻¹) with sub-10 ppm detection and quantification limits. The MIP-QCM sensor also exhibits a 6-fold higher sensitivity compared to the NIP-QCM, and a dynamic working range of 30–100 ppm. The response time of MIP-QCM devices for a single cycle of analyte adsorption, signal saturation, and MIP regeneration is less than 2.5 min. The sensor also demonstrates selectivity factors of artemether-MIP of 2.2 and 4.1 compared to artemisinin and lumefantrine, respectively. Reversibility tests reveal less than 5% variation in sensor responses over three cycles of measurements at each tested concentration. The MIP-QCM showed lower detection limits than conventional HPLC-UV, and faster response time compared to HPLC-UV and liquid chromatography-mass spectrometry (LC-MS).

Chemical structures of the antimalarial drugs: artemisinin, artemether (a methyl ether derivative of artemisinin), and lumefantrine.     

The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective

Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at the N-terminal binding domain (NTD) of the spike protein, must be studied in depth to devise new therapeutic options. Structural variants reported in the RBD and NTD may play essential roles in the increased pathogenicity of this SARS-CoV-2 new variant. We explored the binding differences and structural-dynamic features of the B.1.618 variant using structural and biomolecular simulation approaches. Our results revealed that the E484K mutation in the RBD slightly altered the binding affinity through affecting the hydrogen bonding network. We also observed that the flexibility of three important loops in the RBD required for binding was increased, which may improve the conformational optimization and consequently binding of the new variant. Furthermore, we found that deletions of Tyr145 and His146 at the NTD reduced the binding affinity of the monoclonal antibody (mAb) 4A8, and that the hydrogen bonding network was significantly affected consequently. This data show that the new B.1.618 variant is an antibody-escaping variant with slightly altered ACE2–RBD affinity. Moreover, we provide insights into the binding and structural-dynamics changes resulting from novel mutations in the RBD and NTD. Our results suggest the need for further in vitro and in vivo studies that will facilitate the development of possible therapies for new variants such as B.1.618.

This study explored the binding patterns of the wild type and B.1.618 variant using which revealed that the B.1.618 variant possess a stronger binding affinity for the host ACE2 and escape the neutralizing antibodies.     

Outpatient Vascular Intervention: A Two-Year Experience

PURPOSE: To retrospectively analyze the outcome of a range of interventional vascular procedures performed on outpatients. METHODS: Suitability for outpatient procedures was assessed according to agreed protocols. An episode was defined as any procedure/s through a single access site at one attendance. Retrospective case-note review was performed. RESULTS: There were 693 outpatient episodes between April 1998 and May 2000 (290 interventional, and 403 diagnostic procedures), comprising 25% (693/2,769) of the total workload. Follow-up is available in 214; 38 of these were transfers from outlying hospitals and were excluded from analysis. One hundred and seventy-six were true outpatients. There were 98 iliac and 46 femoropopliteal interventions, 2 aortic stents, 1 renal and 5 upper-limb angioplasties (PTAs), 5 embolizations, 8 Hickman lines, 1 line stripping, 3 atherectomies, 1 dialysis-graft PTA and 6 bypass-graft PTAs. Sixty-eight closure devices were used. Twelve patients were converted to inpatients (6.8%, 12/176). The readmission rate was 3.4% (6/176). The reattendance rate was 1.1% (2/176), both subsequently attending for outpatient duplex ultrasound examination to exclude pseudoaneurysm. The major complication rate was 3.4% and the delayed major complication rate was 1.7%. CONCLUSION: Outpatient vascular intervention is safe with appropriate protocols and with careful patient selection. Local vascular services benefit from the release of inpatient beds.     

Association between complementary feeding practice and mothers education status in Islamabad

OBJECTIVES: To examine the association between mother's education, complementary feeding practices and malnutrition amongst mothers attending outpatient clinics in Islamabad. METHODS: Mothers of 500 Pakistani infants attending the Paediatric Outpatient department at the Federal Government Services Hospital, Islamabad completed pretested questionnaires on mother's educational status and complementary feeding practices. RESULTS: A positive relationship was found between the nutritional status of infants and educational status of mothers (P < 0.001). The study revealed that the majority of infants with evidence of malnutrition belonged to the mothers with virtually no school education. A similar relationship was observed between the educational status of respondents and the introduction of complementary foods at an appropriate age (6 months) of infants (P < 0.001). CONCLUSION: Mother's education plays a vital role in increased receptivity to knowledge and awareness related to nutritional requirements of their infants.     

Purunusides A-C, α-glucosidase inhibitory homoisoflavone glucosides from <Emphasis Type="Italic">Prunus domestica</Emphasis>

Purunusides A-C (1–3), new homoisoflavone glucosides together with the known compounds β-sitosterol (4) and 6,7-methylenedioxy-8-methoxycoumarin (5) have been isolated from n-butanol and ethyl acetate soluble fractions of Prunus domestica. Their structures were assigned on the basis of spectral studies. The compounds 1–3 showed potent inhibitory activity against the enzyme α-glucosidase.     

Assessment of Trace Metal and Metalloid Accumulation and Human Health Risk from Vegetables Consumption through Spinach and Coriander Specimens Irrigated with Wastewater

This study focused on evaluating the metal and metalloid contamination and associated risks in the two vegetables crops, coriander (Coriandrum sativum) and spinach (Spinacia oleracea) treated with three water regimes, canal water, groundwater and municipal wastewater. These vegetables are widely consumed by people and are also used in traditional medicine for treating various disorders. Metal and metalloid accumulation (Zn, Pb, Se, Cu, As, Mo, Fe, Ni) was found higher in vegetables treated with wastewater. Wastewater treated soil had high pollution load index. Fe, Zn, As and Pb had higher values in water, soil and vegetables as compared to other studied metals. Overall, metal correlation for soil and vegetables was significant and positive except for Fe and Cu in spinach. The highest value for daily metal intake was estimated for Fe while Se had the lowest value for the same index. It was thus concluded that trace metal and metalloid accumulation was a major health concern for the public consuming these vegetables.     

Human diseases,immunity and the oral microbiota—Insights gained from metagenomic studies

The immune system consists of a complex but organised myriad of cell types that continually maintain and survey their resident environment. It is this balanced homeostatic relationship between the cells of the immune system and its surrounding environment that shapes the microbial flora. In the oral cavity, the immune system not only has to harmonise with the ecology of commensal bacteria, fungi and viruses but also should be able to defend against pathogenic microbes. In fact, the oral microbiota is altered in situations when the immune system is dysregulated. There are a number of human diseases or conditions that perturb the balance of the host immune system and have an effect on the host oral microbiota. If this balance is disturbed, the symbiotic relationship will shift to allow the colonisation or overgrowth of potentially pathogenic species, inducing a pathogenic process that leads to various disease symptoms. The dynamics balance between the immune status and the oral microbial community of an individual has remained understudied till recently. Advances in metagenomics allow detailed investigations into oral microbial population and the possible diversity. This concise review summarises the current findings using metagenomic approaches for studying oral microbial flora diversity.     

Convenient pH-responsive removal of Acid Black 1 by green l-histidine/iron oxide magnetic nanoadsorbent from water: performance and mechanistic studies

This study was aimed at developing green histidine-modified Fe₃O₄ nanoparticles (His-MNPs) for the adsorptive removal of Acid Black 1 (AB1) from aqueous solution. The His-MNPs were characterized by atomic force microscopy, scanning electron microscopy-energy dispersive X-ray spectrometry, infra-red spectra and thermogravimetry. These MNPs were spherical (average diameter 11–28 nm) with polydispersity index of 1.40 and about 13% mass coating of histidine. To optimize AB1 adsorption on His-MNPs and understand its mechanism, the influences of different operational variables (pH, adsorbent amount, temperature, initial AB1 concentration, contact time, ionic strength, etc.) on adsorption were examined with adsorption isotherms, kinetics and thermodynamic studies. The AB1 adsorption from water was fast with equilibrium time ≤ 45 min. The adsorption equilibrium was best fitted to the Langmuir isotherm model (q_max = 166.7 mg g⁻¹ at the adsorbent dose of 0.2 g L⁻¹, temperature 30 °C and pH 4). The linearity order for other isotherms was as follows: Dubinin–Radushkevich (D–R) < Temkin < Freundlich. The kinetics of the AB1 adsorption demonstrated the best compliance with the pseudo-second-order model, predominantly controlled by film diffusion as compared to intraparticle diffusion. Thermodynamic parameters (ΔH° and ΔG°) reflected the exothermic and spontaneous adsorption process. The values of ΔG°, ΔH°, activation energy and D–R free adsorption energy were all consistent with the physisorptive removal of AB1. The spectral (electronic and IR) and pH studies further corroborated the mechanism of AB1 removal by His-MNPs. The His-MNPs showed efficient adsorption, easy regeneration and excellent reusability, assisted by their pH-responsive properties. The prepared adsorbent can provide a safe, effective and economical alternative strategy for removing azo dyes from wastewater.

Effective and eco-friendly separation of Acid Black 1 dye from water by electrostatic adsorption onto reusable Histidine-Fe₃O₄ nanoparticles, credited to their pH-responsiveness.