Transforming microbial pigment into therapeutic revelation: extraction and characterization of pyocyanin from Pseudomonas aeruginosa and its therapeutic potential as an antibacterial and anticancer agent.

BACKGROUND: The objectives of the current study were to extract pyocyanin from Pseudomonas aeruginosa clinical isolates, characterize its chemical nature, and assess its biological activity against different bacteria and cancer cells. Due to its diverse bioactive properties, pyocyanin, being one of the virulence factors of P. aeruginosa, holds a promising, safe, and available therapeutic potential. METHODS: 30 clinical P. aeruginosa isolates were collected from different sources of infections and identified by routine methods, the VITEK 2 compact system, and 16 S rRNA. The phenazine-modifying genes (phzM, phzS) were identified using polymerase chain reaction (PCR). Pyocyanin chemical characterization included UV-Vis spectrophotometry, Fourier Transform Infra-Red spectroscopy (FTIR), Gas Chromatography-Mass Spectrometry (GC-MS), and Liquid Chromatography-Mass Spectrometry (LC-MS). The biological activity of pyocyanin was explored by determining the MIC values against different clinical bacterial strains and assessing its anticancer activity against A549, MDA-MB-231, and Caco-2 cancer cell lines using cytotoxicity, wound healing and colony forming assays. RESULTS: All identified isolates harboured at least one of the phzM or phzS genes. The co-presence of both genes was demonstrated in 13 isolates. The UV-VIS absorbance peaks were maxima at 215, 265, 385, and 520 nm. FTIR could identify the characteristic pyocyanin functional groups, whereas both GC-MS and LC-MS elucidated the chemical formula C11H18N2O2, with a molecular weight 210. The quadri-technical analytical approaches confirmed the chemical nature of the extracted pyocyanin. The extract showed broad-spectrum antibacterial activity, with the greatest activity against Bacillus, Staphylococcus, and Streptococcus species (MICs 31.25-125 µg/mL), followed by E. coli isolates (MICs 250-1000 µg/mL). Regarding the anticancer activity, the pyocyanin extract showed IC50 values against A549, MDA-MB-231, and Caco-2 cancer cell lines of 130, 105, and 187.9 µg/mL, respectively. Furthermore, pyocyanin has markedly suppressed colony formation and migratory abilities in these cells. CONCLUSIONS: The extracted pyocyanin has demonstrated to be a potentially effective candidate against various bacterial infections and cancers. Hence, the current findings could contribute to producing this natural compound easily through an affordable method. Nonetheless, future studies are required to investigate pyocyanin's effects in vivo and analyse the results of combining it with other traditional antibiotics or anticancer drugs.

Methylphenidate, but not citalopram, decreases impulsive choice in rats performing a temporal discounting task.

Introduction: Drugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine reuptake can modulate distinct aspects of impulsivity - though such tests are often performed using distinct behavioral tasks prohibiting easy comparisons. Methods: Here, we directly compare pharmacologic agents that affect dopamine (methylphenidate) vs serotonin (citalopram) manipulations on choice impulsivity in a temporal discounting task where rats could choose between a small, immediate reward or a large reward delayed at either 2 or 10s. In control conditions, rats preferred the large reward at a small (2s) delay and discounted the large reward at a long (10s) delay. Results: Methylphenidate, a dopamine transport inhibitor that blocks reuptake of dopamine, dose-dependently increased large reward preference in the long delay (10s) block. Citalopram, a selective serotonin reuptake inhibitor, had no effect on temporal discounting behavior. Impulsive behavior on the temporal discounting task was at least partially mediated by the nucleus accumbens shell. Bilateral lesions to the nucleus accumbens shell reduced choice impulsivity during the long delay (10s) block. Following lesions, methylphenidate did not impact impulsivity. Discussion: Our results suggest that striatal dopaminergic systems modulate choice impulsivity via actions within the nucleus accumbens shell, whereas serotonin systems may regulate different aspects of behavioral inhibition/impulsivity.

Behavioral Interventions Can Improve Brain Injury-Induced Deficits in Behavioral Flexibility and Impulsivity Linked to Impaired Reward-Feedback Beta Oscillations.

Traumatic brain injury (TBI) affects a large population, resulting in severe cognitive impairments. Although cognitive rehabilitation is an accepted treatment for some deficits, studies in patients are limited in ability to probe physiological and behavioral mechanisms. Therefore, animal models are needed to optimize strategies. Frontal TBI in a rat model results in robust and replicable cognitive deficits, making this an ideal candidate for investigating various behavioral interventions. In this study, we report three distinct frontal TBI experiments assessing behavior well into the chronic post-injury period using male Long-Evans rats. First, we evaluated the impact of frontal injury on local field potentials recorded simultaneously from 12 brain regions during a probabilistic reversal learning (PbR) task. Next, a set of rats were tested on a similar PbR task or an impulsivity task (differential reinforcement of low-rate behavior [DRL]) and half received salient cues associated with reinforcement contingencies to encourage engagement in the target behavior. After intervention on the PbR task, brains were stained for markers of activity. On the DRL task, cue relevance was decoupled from outcomes to determine if beneficial effects persisted on impulsive behavior. TBI decreased the ability to detect reinforced outcomes; this was evident in task performance and reward-feedback signals occurring at beta frequencies in lateral orbitofrontal cortex (OFC) and associated frontostriatal regions. The behavioral intervention improved flexibility and increased OFC activity. Intervention also reduced impulsivity, even after cues were decoupled, which was partially mediated by improvements in timing behavior. The current study established a platform to begin investigating cognitive rehabilitation in rats and identified a strong role for dysfunctional OFC signaling in probabilistic learning after frontal TBI.

In-lab synthesized turn-off fluorescence sensor for estimation of Gemigliptin and Rosuvastatin polypill appraised by Spider diagram, AGREE and whiteness metrics.

Gemigliptin-Rosuvastatin single-pill combination is a promising therapeutic tool in the effective control of hyperglycemia and hypercholesterolemia. Organic sensors with high quantum yields have profoundly significant applications in the pharmaceutical industry, such as routine quality control of marketed formulations. Herein, the fluorescence sensor, 2-Morpholino-4,6-dimethyl nicotinonitrile 3, (λex; 226 nm, λem; 406 nm), was synthesized with a fluorescence quantum yield of 56.86% and fully characterized in our laboratory. This sensor showed high efficiency for the determination of Gemigliptin (GEM) and Rosuvastatin (RSV) traces through their stoichiometric interactions and simultaneously fractionated by selective solvation. The interaction between the stated analytes and sensor 3 was a quenching effect. Various experimental parameters and the turn-off mechanism were addressed. The adopted approach fulfilled the ICH validation criteria and showed linear satisfactory ranges, 0.2-2 and 0.1-1 µg/mL for GEM and RSV, respectively with nano-limits of detection less than 30 ng/mL for both analytes. The synthesized sensor has been successfully applied for GEM and RSV co-assessment in their synthetic polypill with excellent % recoveries of 98.83 ± 0.86 and 100.19 ± 0.64, respectively. No statistically significant difference between the results of the proposed and reported spectrophotometric methods in terms of the F- and t-tests. Ecological and whiteness appraisals of the proposed study were conducted via three novel approaches: the Greenness Index via Spider Diagram, the Analytical Greenness Metric, and the Red-Green-Blue 12 model. The aforementioned metrics proved the superiority of the adopted approach over the previously published one regarding eco-friendliness and sustainability. Our devised fluorimetric turn-off sensing method showed high sensitivity, selectivity, feasibility, and rapidity with minimal cost and environmental burden over other sophisticated techniques, making it reliable in quality control labs.

Factors associated with adherence to antiretroviral therapy in HIV-infected subjects and the use of indicators to characterize the treatment adhesion profile.

At present, there is no gold standard to assess patient adherence to combination antiretroviral therapy (cART). Therefore, this study aimed to characterize the epidemiological profile, delineate adherence indicators, and identify factors associated with adherence and delays in obtaining medication in patients registered at the Specialized Assistance Service in HIV/AIDS in Brazil. This is a descriptive study based on secondary data obtained from official databases of the Brazilian Ministry of Health. Adherence and delay were measured by the frequency of cART medication acquisition in 24 months, and a multivariate linear regression model was developed to identify the factors associated with non-adherence and delays. In 50.2% of the subjects, the viral load remained undetectable throughout the study period. Only 12.4% of patients were fully adherent to cART. Regarding indicators, a value of 0.83 was found for adherence, 0.09 for delay in days, and 0.21 for the number of times the patient was late to obtain the medication. The multivariate analysis showed that males, age between 20 and 59 years, having not changed the cART, and the presence of ≥1000 HIV RNA copies/mL were predictive factors for adherence and delays (P≤0.01). We demonstrated that monitoring cART medication distribution is possible using health indicators, and identifying the factors associated with poor adherence to cART helps characterize patients at higher risks of unsuccessful therapy.

Green and Smart Quantitative Quality Control for Veterinary Mixture of Ivermectin and Clorsulon: Ecological Evaluation of Spectral Analyses via Analytical Eco-Scale, Green Analytical Procedure Index, and Analytical GREEnness Metric Approaches.

BACKGROUND: The global financial market is still highly threatened by bovine fasciolosis, a parasitic infection that targets cattle, mainly in tropical regions. Binary combination of ivermectin (IVER) and clorsulon (CLO), in challenging concentration ratios, is typically indicated for treatment and control of fasciolosis. OBJECTIVE: The present study aims at smart simultaneous spectrophotometric assay of both compounds at their high ratio in marketed formulation and synthetic mixtures, without any prior separation. Furthermore, their greenness profile was evaluated and compared with previous reported assay methods, including the official one. METHODS: Mathematical-based proposed methods are the dual-wavelength, induced dual-wavelength, and first derivative ratio methods. Each is developed, optimized, and applied to determine simultaneously IVER and CLO at linear ranges of 1-30 and 5-40 µg/mL, respectively. They have been validated according to ICH guidelines. Statistical Student t-tests and F-tests compared the proposed methods with a USP chromatographic technique. Ecological appraisal is accomplished using three independent metrics: Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI), and Analytical GREEnness Metric Approach (AGREE). RESULTS: Satisfactory recoveries, ICH compliance, and adherence of proposed methods to the ecological safety margin are achieved. CONCLUSIONS: Developed methods are eco-friendly and cost-effective and can accomplish a routine quantitative quality control for concurrent determination of both drugs. HIGHLIGHTS: Veterinary antimicrobials need analytical quality control using safer and green methodologies. Data manipulated spectral analyses of IVER and CLO, in a ratio of 1:10% (v/v), are developed and optimized. AES, GAPI, and AGREE approaches illustrate the high green compliance in respect to assays reported in the literature. Furthermore, the United States Pharmacopeia (USP) assay for IVER and CLO in injectable dosage form depends on analysis of each drug separately in the presence of the other drug, but it cannot determine both drugs simultaneously.

Critical Beginnings: Selective Tuning of Solubility and Structural Accuracy of Newly Synthesized Proteins by the Hsp70 Chaperone System.

Proteins are particularly prone to aggregation immediately after release from the ribosome, and it is therefore important to elucidate the role of chaperones during these key steps of protein life. The Hsp70 and trigger factor (TF) chaperone systems interact with nascent proteins during biogenesis and immediately post-translationally. It is unclear, however, whether these chaperones can prevent formation of soluble and insoluble aggregates. Here, we address this question by monitoring the solubility and structural accuracy of globin proteins biosynthesized in an Escherichia coli cell-free system containing different concentrations of the bacterial Hsp70 and TF chaperones. We find that Hsp70 concentrations required to grant solubility to newly synthesized proteins are extremely sensitive to client-protein sequence. Importantly, Hsp70 concentrations yielding soluble client proteins are insufficient to prevent formation of soluble aggregates. In fact, for some aggregation-prone protein variants, avoidance of soluble-aggregate formation demands Hsp70 concentrations that exceed cellular levels in E. coli. In all, our data highlight the prominent role of soluble aggregates upon nascent-protein release from the ribosome and show the limitations of the Hsp70 chaperone system in the case of highly aggregation-prone proteins. These results demonstrate the need to devise better strategies to prevent soluble-aggregate formation upon release from the ribosome.

Assessing the impact of community-based interventions on hypertension and diabetes management in three Minnesota communities: Findings from the prospective evaluation of US HealthRise programs.

BACKGROUND: Community-based health interventions are increasingly viewed as models of care that can bridge healthcare gaps experienced by underserved communities in the United States (US). With this study, we sought to assess the impact of such interventions, as implemented through the US HealthRise program, on hypertension and diabetes among underserved communities in Hennepin, Ramsey, and Rice Counties, Minnesota. METHODS AND FINDINGS: HealthRise patient data from June 2016 to October 2018 were assessed relative to comparison patients in a difference-in-difference analysis, quantifying program impact on reducing systolic blood pressure (SBP) and hemoglobin A1c, as well as meeting clinical targets (< 140 mmHg for hypertension, < 8% Al1c for diabetes), beyond routine care. For hypertension, HealthRise participation was associated with SBP reductions in Rice (6.9 mmHg [95% confidence interval: 0.9-12.9]) and higher clinical target achievement in Hennepin (27.3 percentage-points [9.8-44.9]) and Rice (17.1 percentage-points [0.9 to 33.3]). For diabetes, HealthRise was associated with A1c decreases in Ramsey (1.3 [0.4-2.2]). Qualitative data showed the value of home visits alongside clinic-based services; however, challenges remained, including community health worker retention and program sustainability. CONCLUSIONS: HealthRise participation had positive effects on improving hypertension and diabetes outcomes at some sites. While community-based health programs can help bridge healthcare gaps, they alone cannot fully address structural inequalities experienced by many underserved communities.

Carbon dots as fluorescent nanoprobes for assay of some non-fluorophoric nitrogenous compounds of high pharmaceutical interest.

Background: Carbon dots, CDs, have excellent photoluminescence properties, good biocompatibility, low toxicity and good light stability. The optical, magnetic and electronic properties of CDs make them a hugely relevant tool to be used in pharmaceutical analysis, bioimaging, drug delivery, and other fields. The fluorescence of carbon nanodots makes it suitable for assay of some nitrogenous compounds of high pharmaceutical interest. In this work, we develop simple, fast and green spectrophotometric methods for quantification of Azithromycin and Rasagiline mesilate using synthesized fluorescent CDs from garlic peels. Results: The spectrometric methods depend on stoichiometric reactions of both drugs with fluorescent CDs. Carbon dots exhibit a declared absorption peak λmax at 238 nm and potent fluorimetric emission at λem 528 nm, upon excitation at λex 376 nm. Drugs' concentrations in ppm are efficiently calculated using Stern-Volmer Equation. Decrease in fluorescence (ΔF = F o - F) and the F-ratio values are linearly correlated to molar concentration of each quencher (drug). A significant linear diminish in the dots' measured absorbance and fluorimetric emission values was observed. Validation of all the developed methods was according to the ICH guidelines. Conclusions: In a new way, this work successfully indicates, spectrometric methods for rapid detection of two non-fluorophoric nitrogenous compounds using potent carbon nanodots. Consequently, these green developed methods offer several benefits as simplicity, ease of quantification, accuracy and precision that encourage the application of the developed methods in routine analysis of Azithromycin and Rasagiline mesilate in quality control laboratories as analytical tool. Supplementary Information: The online version contains supplementary material available at 10.1186/s43088-023-00346-z.

Experiences of receiving an increased chance of sex chromosome aneuploidy result from non-invasive prenatal testing in Australia: "A more complicated scenario than what I had ever realized".

Many non-invasive prenatal testing (NIPT) platforms screen for sex chromosome aneuploidy (SCA) and SCA analysis is generally included in Australia where NIPT is available as a self-funded test. Little is known about the experience of receiving an NIPT result indicating an increased chance of SCA. This study aimed to explore the experiences of people who received this result and their perspectives on the information, care, and support they received from healthcare practitioners (HCPs). Semi-structured interviews were conducted with people who received an NIPT result indicating an increased chance of SCA and continued their pregnancy. Most participants only had contact with a genetic counselor after receiving their result. Transcribed data were analyzed using rigorous thematic analysis to identify important patterns and themes. Participants (18 women, 2 male partners) described embarking on NIPT, primarily based on advice from their HCP and without much consideration. Consequently, participants expressed feeling unprepared for the unanticipated complexity of their NIPT result and were faced with making a time-sensitive decision about a condition they had not previously considered. While more pre-test information was desired, timely access to genetic counseling post-test assisted with adjustment to the result. These findings suggest that routinization of NIPT may be compromising informed decision-making, resulting in unpreparedness for an increased chance result. Given the increasing uptake and expanding scope of NIPT, resources should be dedicated to educating HCPs offering NIPT and ensuring timely access to genetic counseling post-result. With appropriate funding, genetics services may be able to play a central role in offering information and support to both people who undertake NIPT and their HCPs ordering the testing. Implementing a publicly funded screening program in Australia could assist with standardizing prenatal screening care pathways and consequently better access to appropriate resources.

Theoretical and experimental approach of fuel gas and carbon black production from coal tar pitch by thermal plasma process.

The processing of coal tar pitch (CTP) to produce clean fuel gas and carbon black (CB) is studied in a plasma reactor equipped with a direct-current plasma torch. The composition of the gas produced and energy costs were estimated theoretically for the CTP pyrolysis and gasification processes by two oxidants, namely oxygen and water vapor. We have found that the main gaseous compounds obtained in the pyrolysis and gasification processes are hydrogen (H2), carbon monoxide (CO), and very often carbon dioxide (CO2). For the pyrolysis case, the mean value of the synthesis gas concentration reaches a major value of 98 vol.% (H2 - 81 vol.%, CO - 17. vol.%). However, only 23% of the initial CTP is transformed into gas phase at 1100 K and its content increases up to 37.4% at a temperature of 3000 K. For oxygen gasification, the syngas quantity is little less compared to the pyrolysis case and attains 96.6 vol.% (H2 - 26.5 vol.%, CO - 70.1 vol.%) for T > 1100 K. An intermediate syngas content for the water steam gasification is 97.8 vol.% (with H2 - 55.8 vol.% and CO - 42.0 vol.%). The CB produced was composed of well-defined spherical particles of 30-nm size. Furthermore, it is composed of carbon (98.2%), and followed by oxygen (1.8%) with a surface area of 97 m2 g-1. The thermal plasma system shows high efficiency in conversion of CTP into high-value-added products.

Factors associated with adherence to antiretroviral therapy in HIV-infected subjects and the use of indicators to characterize the treatment adhesion profile

At present, there is no gold standard to assess patient adherence to combination antiretroviral therapy (cART). Therefore, this study aimed to characterize the epidemiological profile, delineate adherence indicators, and identify factors associated with adherence and delays in obtaining medication in patients registered at the Specialized Assistance Service in HIV/AIDS in Brazil. This is a descriptive study based on secondary data obtained from official databases of the Brazilian Ministry of Health. Adherence and delay were measured by the frequency of cART medication acquisition in 24 months, and a multivariate linear regression model was developed to identify the factors associated with non-adherence and delays. In 50.2% of the subjects, the viral load remained undetectable throughout the study period. Only 12.4% of patients were fully adherent to cART. Regarding indicators, a value of 0.83 was found for adherence, 0.09 for delay in days, and 0.21 for the number of times the patient was late to obtain the medication. The multivariate analysis showed that males, age between 20 and 59 years, having not changed the cART, and the presence of ≥1000 HIV RNA copies/mL were predictive factors for adherence and delays (P≤0.01). We demonstrated that monitoring cART medication distribution is possible using health indicators, and identifying the factors associated with poor adherence to cART helps characterize patients at higher risks of unsuccessful therapy.

Quantification of 16 cephalosporins in the aquatic environment by liquid chromatography-tandem mass spectrometry.

Antimicrobial agents are essential to protect human and animal health. During the coronavirus disease 2019 pandemic, antimicrobials such as cephalosporins were widely used as prophylactics and to prevent bacterial co-infection. Undoubtedly, the prevalence of antibiotics in the aquatic environment will ultimately affect the degree of resistance against these bacteria in animals and the environmental systems. In order to monitor 16 cephalosporins in the aquatic environment, we developed a new liquid chromatography-tandem mass spectrometry method that functioned simultaneously under positive and negative electrospray ionization switching modes. The chromatographic separation has been implemented using a pentafluorophenyl propyl column kept at 40°C. The limits of detection and quantitation for the studied cephalosporins ranged from (8 × 10-4 ) to (7.11 × 10-2 ) ng/ml and from (2.61 × 10-3 ) to (2.37 × 10-1 ) ng/ml, respectively. The percent extraction efficiency (apparent recovery) and relative standard deviations for the analyzed cephalosporins ranged from 61.69% to 167.67% and 2.45% to 13.48%, respectively. The overall findings showed that the effluent from the wastewater treatment plants that receive wastewater from pharmaceutical factories had a higher detected amount of cephalosporins than that of domestic sewage. Moreover, seven cephalosporins, including cefuroxime, ceftazidime, cefradine, cefprozil, cefixime, cefalexin, and cefadroxil (0.68-105.45 ng/L) were determined in the aquatic environment.

Providing Contraceptive Health Services to Adolescents and Young Adults by Telemedicine: A Scoping Review of Patient and Provider Perspectives.

OBJECTIVE: The objective of this scoping review is to synthesize and identify gaps in existing research on accessibility of telemedicine-delivered contraceptive health services to female adolescents and young adults (AYAs) and acceptability of these services to AYA patients and their medical providers. METHODS: We searched the PubMed, Scopus, Embase, and CINAHL databases to extract relevant studies on telemedicine and provision of contraceptive services among non-institutionalized, non-chronically ill female AYAs, ages 10 through 24 years. RESULTS: We screened 154 articles, and 6 articles representing 5 studies met the full inclusion criteria. Three studies assessed telemedicine acceptability and accessibility from the perspective of providers, and 3 described patients' perceived accessibility and acceptability of a theoretical telemedicine visit. No studies directly assessed AYA patients' satisfaction with actual telemedicine visits for contraceptive services. Providers viewed telemedicine-delivered sexual and reproductive health (SRH) services as acceptable to themselves and AYA patients. Most AYAs reported that they would use telemedicine for SRH services, although they would prefer in-person care. All articles identified concerns about privacy and confidentiality as a barrier to SRH telemedicine care. CONCLUSIONS: Telemedicine-delivered contraceptive health services for AYAs were perceived as acceptable and accessible by providers and by most AYA patients, although patients reported a preference for in-person care. However, none of these findings are based on patients' actual experiences with SRH telemedicine. Further research is needed to directly assess the accessibility and acceptability of telemedicine-delivered contraceptive health services for female AYA patients.

Protein folding in vitro and in the cell: From a solitary journey to a team effort.

Correct protein folding is essential for the health and function of living organisms. Yet, it is not well understood how unfolded proteins reach their native state and avoid aggregation, especially within the cellular milieu. Some proteins, especially small, single-domain and apparent two-state folders, successfully attain their native state upon dilution from denaturant. Yet, many more proteins undergo misfolding and aggregation during this process, in a concentration-dependent fashion. Once formed, native and aggregated states are often kinetically trapped relative to each other. Hence, the early stages of protein life are absolutely critical for proper kinetic channeling to the folded state and for long-term solubility and function. This review summarizes current knowledge on protein folding/aggregation mechanisms in buffered solution and within the bacterial cell, highlighting early stages. Remarkably, teamwork between nascent chain, ribosome, trigger factor and Hsp70 molecular chaperones enables all proteins to overcome aggregation propensities and reach a long-lived bioactive state.

Evaluation of thermal plasma process for treatment disposal of solid radioactive waste.

The management of radioactive waste is a worldwide activity based on the guidelines of the International Atomic Energy Agency (IAEA), and all stages of management require scientifically proven methods for possible deployment. The management of radioactive waste is a huge challenge due to the high risk in the collection, gathering, transport, handling, and storage. In this study, a thermal plasma treatment process was evaluated for its efficiency to process solid radioactive waste. Experiments were carried out with the application of stable isotopes of Lead, Iodine, Cobalt, and Cesium. After the thermal plasma treatments, the slag and the residual gas were analyzed to verify the influence of process time and discharge power on the efficiency of the process. The treatment for 25 min and 10 kW was sufficient to reduce the mass by 50% of the slag. When the applied power was increased to 15 kW, an expressive reduction in the treatment time (10 min) was able to promote the same mass reduction. The results indicated that the treatment of radioactive waste by thermal plasma is a promising method to manage and reduce the mass and volume for the final disposal.

Comparative Greenness Metric Estimates for Content Uniformity Testing of Anti-Cov-2, GS-5734 in Commercial Vials: Validated Micellar Electrokinetic Chromatographic Assay.

BACKGROUND: The antiviral drug GS-5734 remdesivir is a new phosphoramidate prodrug developed initially as a treatment for Ebola virus which then proved to have antiviral properties against other viruses. After clinical trials, it was the first antiviral to be approved by the U.S. Food and Drug Administration in 2020 to treat severe coronavirus (COVID-19) cases. The widespread current pandemic gave an urge to its fast production and marketing. Thus, new analytical methods must be available for its analysis in a fast and easy manner with low cost to be applicable in all laboratories. OBJECTIVE: In the current study, a green and economic micellar electrokinetic chromatographic (MEKC) method is proposed for remdesivir analysis. METHODS: A fused-silica capillary (58.5 cm × 50 µm id, 50 cm effective length) with 20 mM borate buffer (pH 9) and 25 mM sodium dodecyl sulfate was used under a positive potential of 30 kV at 25°C with detection at 245 nm. RESULTS: Remdesivir analysis was achieved in approximately 5 min. The method proved to be linear in range of 1-50 µg/mL with correlation coefficient, r > 0.999. CONCLUSION: The MEKC method proposed was applied to the analysis of remdesivir in its commercial vials. The method was validated per International Conference on Harmonization guidelines. HIGHLIGHTS: Green chemistry has been the focus of the analytical community in the past few years. This method is considered green due to its low energy and solvent consumption without sacrificing the method's sensitivity or selectivity. The method's green profile has been assessed by different greenness assessment scales to ensure the method is eco-friendly and can be used in the pharmaceutical industry.

The impact of the COVID-19 pandemic on perceived access to health care and preferences for health care provision in individuals (being) treated for breast cancer.

PURPOSE: To evaluate perceived access to health care and preferences for health care provision among patients (being) treated for breast cancer during the COVID-19 pandemic. METHODS: Longitudinal study within the prospective, multicenter UMBRELLA cohort of patients (being) treated for breast cancer. All cohort participants enrolled in UMBRELLA between October 2013 and November 2020 were sent a COVID-19-specific survey during the first and second wave of the COVID-19 pandemic, i.e., April 2020 and November 2020, respectively. RESULTS: In total, 1106 (69.3%) and 822 (50.9%) cohort participants completed the survey in the first and second wave, respectively. The proportion of patients experiencing that their treatment or follow-up care was affected due to COVID-19 decreased from 28.4% (n = 198) in April 2020 to 14.8% (n = 103) in November 2020. Throughout the pandemic, one or more hospital consultations were postponed in 10.0% (n = 82) of all patients and changed into a teleconsultation in 23.1% (n = 190). The proportion of patients who experienced a higher threshold to contact their general practitioner due to COVID-19 decreased from 29.9% (n = 204) in the first wave to 20.8% (n = 145) in the second wave. In-person consultations remained most preferred in 35.2% (n = 289) of all patients. Nearly half of all patients (48.3%, n = 396) indicated that telehealth would be a useful alternative for in-person consultations in future. CONCLUSION: Perceived access to health care has improved substantially throughout the pandemic. Digital care is well received by patients (being) treated for breast cancer.

Novel Siprulina platensis Bilosomes for Combating UVB Induced Skin Damage.

The recent interest in bioactive compounds from natural sources has led to the evolution of the skin care industry. Efforts to develop biologically active ingredients from natural sources have resulted in the emergence of enhanced skin care products. Spirulina (SPR), a nutritionally enriched cyanobacteria-type microalga, is rich in nutrients and phytochemicals. SPR possesses antioxidant, immunomodulatory, and anti-inflammatory activities. Spirulina-loaded bilosomes (SPR-BS), a novel antiaging drug delivery system, were designed for the first time by incorporation in a lecithin−bile salt-integrated system for bypassing skin delivery obstacles. The optimized BS had good entrapment efficiency, small particle size, optimal zeta potential, and sustained drug release pattern. Blank and SPR-loaded BS formulations were safe, with a primary irritancy index of <2 based on the Draize test. In vivo tests were conducted, and photoprotective antiaging effects were evaluated visually and biochemically by analyzing antioxidant, anti-inflammatory, and anti-wrinkling markers following ultraviolet (UV) B irradiation. Results of biochemical marker analysis and histopathological examination confirmed the superior antiaging effect of SPR-BS compared with SPR. Thus, SPR-loaded BS is a promising nanoplatform for SPR delivery, can be used for treating UV-induced skin damage, and offers maximum therapeutic outcomes.