Cyclic voltammetry and chronoamperometry: mechanistic tools for organic electrosynthesis.

Electrochemical methods offer unique advantages for chemical synthesis, as the reaction selectivity may be controlled by tuning the applied potential or current. Similarly, measuring the current or potential during the reaction can provide valuable mechanistic insights into these reactions. The aim of this tutorial review is to explain the use of cyclic voltammetry and chronoamperometry to interrogate reaction mechanisms, optimize electrochemical reactions, or design new reactions. Fundamental principles of cyclic voltammetry and chronoamperometry experiments are presented together with the application of these techniques to probe (electro)chemical reactions. Several diagnostic criteria are noted for the use of cyclic voltammetry and chronoamperometry to analyze coupled electrochemical-chemical (EC) reactions, and a series of individual mechanistic studies are presented. Steady state voltammetric and amperometric measurements, using microelectrodes (ME) or rotating disk electrodes (RDE) provide a means to analyze concentrations of redox active species in bulk solution and offer a versatile strategy to conduct kinetic analysis or determine the species present during (electro)synthetic chemical reactions.

CircRNAs in diagnosis, prognosis, and clinicopathological features of multiple myeloma; a systematic review and meta-analysis.

Unlike improved treatment response in multiple myeloma (MM), the mortality rate in MM is still high. The study's aim is to investigate the potential role of circRNAs as a new biomarker for diagnosis, prognosis, and clinicopathological features of MM. We identified studies through Web of Science, Scopus, PubMed and ProQuest databases, and Google Scholar to August 2022. The SEN, SPE, PLR, NLR, DOR, and AUC were combined to investigate the diagnostic performance of circRNAs in MM. Also, HR and RR were used for prognostic and clinicopathological indicators, respectively. 12 studies for prognosis, 9 studies about diagnosis, and 13 studies regarding clinicopathological features. The pooled SEN, SPE, DOR, and AUC were 0.82, 0.76, 14.70, and 0.86, respectively for the diagnostic performance of circRNAs. For the prognostic performance, oncogene circRNAs showed a poor prognosis for the patients (HR = 3.71) and tumor suppressor circRNAs indicated a good prognosis (HR = 0.31). Finally, we discovered that dysregulation of circRNAs is associated with poor clinical outcomes in beta-2-microglobulin (RR = 1.56), Durie-Salmon stage (RR = 1.36), and ISS stage (RR = 1.79). Furthermore, the presence of del(17p) and t(4;14) is associated with circRNA dysregulation (RR = 1.44 and 1.44, respectively). Our meta-analysis demonstrates that the expression analysis of circRNAs is valuable for MM's diagnosis and prognosis determination. Also, dysregulation of circRNAs is associated with poor clinicopathological features and can be used as the applicable biomarkers for evaluating treatment effectiveness.

MicroRNA-125b as a valuable predictive marker for outcome after autologous hematopoietic stem cell transplantation.

BACKGROUND: Relapse is a frequent occurrence in autologous hematopoietic stem cell transplantation (AHSCT), and early relapse after AHSCT results in poor survival and low quality of life. Predictive marker determination for AHSCT outcomes could be helpful in the prevention of relapse through personalized medicine. Here the predictive value of circulatory microRNAs (miRs) expression for AHSCT outcomes was studied. METHODS: 50 MM and lymphoma candidates for AHSCT participated in this study. Two plasma samples were obtained before AHSCT from each candidate; one before mobilization and the other after conditioning. Extracellular vesicles (EVs) were isolated by ultracentrifugation. miR-125b, miR-126, miR-150, and miR-155 expression were analyzed in both plasma and EVs using real time polymerase chain reaction analysis. Other data related to AHSCT and its outcomes were also collected. The predictive value of miRs and other factors for outcomes was assessed by multi-variant analysis. RESULTS: By 90 weeks follow up after AHSCT, multi-variant and ROC analysis showed miR-125b as a predictive marker for relapse, high lactate dehydrogenase (LDH), and high erythrocyte sedimentation rate (ESR). The cumulative incidence of relapse, high LDH, and high ESR increased with an increase in circulatory miR-125b expression. CONCLUSION: miR-125b could be applicable in prognosis evaluation and also create a possible new targeted therapy opportunity for enhanced outcomes and survival after AHSCT. TRIAL REGISTRATION: The study was retrospectively registered. Ethic code No: IR.UMSHA.REC.1400.541.

Human T-cell lymphotropic virus type 1 (HTLV-1) proposed vaccines: a systematic review of preclinical and clinical studies.

BACKGROUND: Numerous vaccination research experiments have been conducted on non-primate hosts to prevent or control HTLV-1 infection. Therefore, reviewing recent advancements for status assessment and strategic planning of future preventative actions to reduce HTLV-1 infection and its consequences would be essential. METHODS: MEDLINE, Scopus, Web of Science, and Clinicaltrials.gov were searched from each database's inception through March 27, 2022. All original articles focusing on developing an HTLV-1 vaccine candidate were included. RESULTS: A total of 47 studies were included. They used a variety of approaches to develop the HTLV-1 vaccine, including DNA-based, dendritic-cell-based, peptide/protein-based, and recombinant vaccinia virus approaches. The majority of the research that was included utilized Tax, Glycoprotein (GP), GAG, POL, REX, and HBZ as their main peptides in order to develop the vaccine. The immunization used in dendritic cell-based investigations, which were more recently published, was accomplished by an activated CD-8 T-cell response. Although there hasn't been much attention lately on this form of the vaccine, the initial attempts to develop an HTLV-1 immunization depended on recombinant vaccinia virus, and the majority of results seem positive and effective for this type of vaccine. Few studies were conducted on humans. Most of the studies were experimental studies using animal models. Adenovirus, Cytomegalovirus (CMV), vaccinia, baculovirus, hepatitis B, measles, and pox were the most commonly used vectors. CONCLUSIONS: This systematic review reported recent progression in the development of HTLV-1 vaccines to identify candidates with the most promising preventive and therapeutic effects.

Responses of activated sludge under a short-term exposure to facial scrub microbeads: implications from treatment performance and higher-life microbial population dynamics.

In this study, four identical laboratory-scale sequencing batch reactors (SBRs) were continuously operated with different concentrations of microbeads (MBs) (5,000-15,000 MBs/L) to investigate the stress-responses of activated sludge under the MB exposure. It was found that the overall treatment performance (organic removal) of SBRs was fairly affected by short-term exposure to low levels of MBs; however, it was adversely affected as the concentration of MBs increased. The average concentration of mixed liquor suspended solids and heterotrophic bacteria in the reactor fed with 15,000 MBs/L were 16 and 30% less than in the pristine control reactor, respectively. Batch experiments further demonstrated that fairly low concentrations of MBs favored the development of dense microbial structures. Further increasing the MB concentrations to 15,000 MBs/L, however, distinctly weakened the settling performance of sludge. Morphological observations revealed suppressed uniformity, strength, and integrity of flocs reactors with the addition of MBs. Microbial community analyses revealed that the abundance of protozoan species declined 37.5, 58, and 64%, respectively, when SBRs were exposed to 5,000; 10,000; and 15,000 MBs/L as compared with the control reactor. The present work provided new insight into the possible effects of MBs on the performances and operational parameters of activated sludge.

Electrosynthesis and Microanalysis in Thin Layer: An Electrochemical Pipette for Rapid Electrolysis and Mechanistic Study of Electrochemical Reactions.

Electrochemistry represents unique approaches for the promotion and mechanistic study of chemical reactions and has garnered increasing attention in different areas of chemistry. This expansion necessitates the enhancement of the traditional electrochemical cells that are intrinsically constrained by mass transport limitations. Herein, we present an approach for designing an electrochemical cell by limiting the reaction chamber to a thin layer of solution, comparable to the thickness of the diffusion layer. This thin layer electrode (TLE) provides a modular platform to bypass the constraints of traditional electrolysis cells and perform electrolysis reactions in the timescale of electroanalytical techniques. The utility of the TLE for electrosynthetic applications benchmarked using NHPI-mediated electrochemical C-H functionalization. The application of microscale electrolysis for the study of drug metabolites was showcased by elucidating the oxidation pathways of the paracetamol drug. Moreover, hosting a microelectrode in the TLE, was shown to enable real-time probing of the profiles of redox-active components of these rapid electrosynthesis reactions.

Electrocatalytic detection of ethanol and acetaldehyde by aminoxyl radicals: utilizing molecular catalysis for breath analysis.

Herein, the insights gleaned from mechanistic studies of aminoxyl catalyzed oxidation of alcohols and aldehydes were used for fabrication of a gas phase sensor for ethanol and acetaldehyde. This electrochemical sensor consists of an aminoxyl radical and graphene oxide so that its response and selectivity can be altered by tuning the basicity of the graphene oxide.

The role of miRNA-377 as a tumor suppressor in lung cancer by negative regulation of genes belonging to ErbB signaling pathway.

BACKGROUND: The ErbB signaling pathway plays important role in the pathogenesis of lung cancer. We explored the role of miRNA-377 as a tumor suppressor in NSCLC through silencing of some genes in the ErbB pathway. METHODS AND RESULTS: The targeting effect of miRNA-377 on EGFR, MAPK1, ABL2, and PAK2 was evaluated. The expression levels of these genes and miRNA-377 were surveyed in NSCLC and normal human tissues, Calu-6, and A549 cells. Real-time PCR was used to figure out whether miRNA-377 could decrease the target genes mRNAs in transfected lung cancer cell lines. The effects of miRNA-377 on apoptosis cell and proliferation were analyzed. We showed that miRNA-377 targets EGFR, MAPK1, and PAK2 mRNAs in in-silico and luciferase reporter assay. The expression of miRNA-377 was significantly downregulated in human NSCLC tissues, Calu-6 and A549 cells compared to their controls. We observed a negative correlation between EGFR, MAPK1, PAK2, and miRNA-377 expression in human NSCLC tissues. A significant reduction in EGFR, MAPK1, and PAK2 mRNA levels was detected, following miRNA-377 transfection in Calu-6 and A549 cells. The higher levels of miRNA-377 in Calu-6, and A549 cells induced apoptosis and reduced proliferation, significantly. CONCLUSIONS: All these data reveal that miRNA-377 functions as a tumor suppressor in NSCLC and may serve as a potential therapeutic target for the treatment of NSCLC.

Enhancement of MBBR reactor efficiency using effective microorganism for treatment of wastewater containing diazinon by engineered Pseudomonas putida KT2440 with manganese peroxidase 2 gene.

Pesticides not only are harmful to humans but they are noxious for water reservoirs, soil, and air quality as well. In this research, diazinon was removed from aqueous solutions by Moving Bed Biofilm Reactor (MBBR). The MBBR was spiked with transgenic Pseudomonas putida KT2440 with Pleurotus ostreatus fungus manganese peroxidase 2 gene to enhance the capabilities of Pseudomonas putida KT2440 in the degradation of diazinon. Although the amount of diazinon and COD and diazinon removal in the reactor including transgenic P. putida KT2440 was 95.46% and 97.47% and they were greater than the control and wild type (non-modified) P. putida KT2440 reactors, the surprising result was related to the adaptation pace of transgenic P. putida KT2440. The produced metabolites and the quantity of diazinon were assessed by HPLC and LC/MS. The metabolite hydroxyisopropyl diazinon was not found in the transgenic P. putida KT2440 reactor. Furthermore, a new sequence of cloned manganese peroxidase 2 gene has been recorded in GenBank with the accession number MT185558. According to bacterial identification of provided sludge the most frequent genus belonged to Aeromonas. Therefore, it seems that the MBBR in the presence of transgenic P. putida KT2440 with manganese peroxidase 2 gene can effectively remove the diazinon.

Health risk assessment of swimming beaches microbial contamination: a case study - Mahmoudabad, Iran.

Waterborne organisms in marine water generally originate from untreated wastewater discharged into the sea. The presence of numerous leisure beaches in Mahmoudabad city, Iran, annually attracts thousands of tourists from all over the country to participate in recreational swimming activities. This study probabilistically characterized the health risks associated with recreational swimming engendered by waterborne pathogens, such as intestinal enterococci and Escherichia coli (E. coli) at 15 sampling points along the beaches of the study using quantitative microbial risk assessment (QMRA). The mean annual infection risk of E. coli in children and adults was 0.424 and 0.229, respectively. The respective risk in terms of enterococci was 0.999 and 0.997, which were higher than the level recommended by the WHO and EPA. The results show that the risk of infection for children was higher than adults. Related authorities have to consider measures to improve environmental quality to protect tourists' and residents' well-being.

Clindamycin removal from aqueous solution by non-thermal air plasma treatment: performance, degradation pathway and ensuing antimicrobial activity.

The present study set out to investigate clindamycin (CLN) removal from aqueous solution using non-thermal plasma (NTP) under atmospheric air conditions and to address the effects of some variables including pH, initial concentration of CLN, and working voltage on CLN degradation. The result showed that the NTP system exhibited excellent degradation rate and mineralization efficiency on CLN in 15 min under neutral conditions, which exceeded 90 and 45%, respectively, demonstrating its conversion to other organic by-products. Furthermore, CLN degradation was largely dependent upon the initial pH of solution, applied voltage, and reaction time. Specifically, under acidic conditions (pH = 3), working voltage of 24 kV and after 15 min of reaction, almost 100% of CLN was degraded. NTP-initiated CLN degradation products through LC-MS/MS analysis, determined within 10 min of reaction, inferred that the complex structure of CLN has undergone deterioration by active radical species which subsequently generated small molecular organic compounds. Chemical processes involved in CLN degradation were found to be demethylation, desulfonylation, dechlorination, hydroxylation and deamination. Lastly, antimicrobial susceptibility tests revealed that the activity of CLN was reduced following NTP treatment, which is also in good agreement with the minimum inhibitory concentration (MIC) values obtained from microdilution analyses.

Exploring Electrosynthesis: Bulk Electrolysis and Cyclic Voltammetry Analysis of the Shono Oxidation.

As electrochemistry continues to gain broader acceptance and use within the organic chemistry community, it is important that advanced undergraduate students are exposed to fundamental and practical knowledge of electrochemical applications for chemical synthesis. Herein, we describe the development of an undergraduate laboratory experience that introduces synthetic and analytical electrochemistry concepts to an advanced organic chemistry class. Experiments focus on the electrooxidative α-functionalization of carbamates, more generally known as the Shono oxidation, and include cyclic voltammetry analysis of two cyclic carbamates and a constant current bulk electrolysis reaction. The exercise offers students an authentic experience in organic electrochemistry, lays a practical and theoretical foundation for future engagement with concepts in electrochemistry and redox chemistry, and strengthens fundamental organic chemistry skills.

Acute promyelocytic leukemia derived extracellular vesicles conserve PML-RARα transcript from storage-inflicted degradation: a stable diagnosis tool in APL patients.

The early death, which is more common in acute promyelocytic leukemia (APL) patients rather than other types of acute myelocytic leukemia (AML) highlights the importance of appropriate diagnostic method for early detection of this disease. The low sensitivity of the conventional methods, low tumor burden in some patients, and the need for bone marrow sampling are some of the diagnostic challenges on the way of proper detection of APL. Given these, we aimed to compare the efficacy of extracellular vesicles (EVs), as a diagnostic tool, with the existing methods. RT-PCR, qPCR, and flow cytometry were applied on EVs and their corresponding associated cellular component collected from 18 APL new cases, 23 patients with minimal residual disease (MRD), and NB4 cell line. RT-PCR results were positive in both cellular and vesicular components of all new cases, NB4 cells, and EVs in contrary to MRD cases. Normalized copy numbers (NCN) of PML-RARα were 5100 and 3950 for cell and EVs, respectively (p < 0.05). There was a significant difference in the NCN of PML-RARα between cells and EVs in BM samples. Investigating the effect of storage at room temperature revealed that PML-RARα level was retained near to the baseline level in EVs, but there was a significant reduction in its copy number in the cellular component during 7 days. Taken together, given to the acceptable stability, EVs could be introduced as a non-invasive liquid biopsy that alongside existing methods could remarkably change the paradigm of APL diagnostic approaches.

Constant Potential and Constant Current Electrolysis: An Introduction and Comparison of Different Techniques for Organic Electrosynthesis.

Electrosynthesis involves transferring charge between two electrodes to promote chemical reactions by applying potential. The modes of controlling the current and potential can affect the reaction mechanism, product distribution and yields, and add a control factor for reaction optimization. In this Synopsis, theoretical discussion is applied to specific case studies from the literature to illustrate methods of adjusting and tracking electrical parameters for the optimization and monitoring of electroorganic reactions.

Analysis of blood donors' characteristics and deferrals related to COVID-19 in Iran.

BACKGROUND: With the outbreak of the coronavirus disease in 2019, called COVID-19, Iranian Blood Transfusion Organization (IBTO) implemented the new deferrals. This study analyzed the COVID-19 deferrals of blood volunteers and compared the demographics, deferrals, and the donor status during the COVID-19 outbreak in 2019. STUDY DESIGN AND METHODS: Data were collected from the integrated blood donor database between Feb-Apr 2019 and 2020. Deferral reasons of COVID-19 were categorized as: those who have symptoms or live with a symptomatic family member, have direct exposure with a confirmed case, have travelled from the outbreak affected areas, and have fully recovered from confirmed COVID-19. The z-test analysis was used, and 95 % confidence intervals were calculated to compare the sample proportions. RESULTS: The blood donations dropped to 26.09 % in 2020. The percent change of first-time blood donors, female donors, and donors within the age group of 45-54 years old was significantly greater in 2020 than the same time frame in 2019 (p < 0.05). The results showed that 0.58 % of volunteers were deferred from blood donation to avoid transmission of SARS-CoV-2. The rate of COVID-19 deferrals in all types except travelling to affected areas has increased in the second 30-day of the study (p < 0.05). CONCLUSION: The blood shortage that occurred during the COVID-19 outbreak was not due to increased deferral for COVID-19, but it was mostly due to a decrease in the number of volunteers who referred to BTCs.

Aspartate Aminotransferase-To-Platelet Ratio Index: a Potential Predictor of Prognosis in the Most Common Types of Cirrhosis.

BACKGROUND: Cirrhosis is often an asymptomatic disease. Its early diagnosis before the development of life-threatening complications is an important step to prevent the progression of the disease. The aim of the present study was the identification of parameters that are significantly changed in cirrhosis, are not affected by the cause of cirrhosis, and are associated with fatal complications of cirrhosis. METHODS: Demographic and pre-transplant ultrasound and laboratory findings were reviewed in patients with viral- (n = 27), autoimmune hepatitis- (n = 27), alcohol- (n = 18), primary sclerosing cholangitis- (PSC) (n = 36), and nonalcoholic steatohepatitis-related cirrhosis (n = 42). RESULTS: Among laboratory findings, only the aspartate aminotransferase-to-platelet ratio index (APRI) value in cirrhotic patients was significantly higher than that of healthy individuals (p < 0.001) and, meanwhile, its value was not different among cirrhotic patients with various etiologies (p = 0.240) but was associated with the ascites, as a cirrhosis life-threatening complication (p < 0.001). CONCLUSIONS: The APRI has acceptable potential to predict prognosis in cirrhosis. So, it can be a possible parameter to the prediction of the lethal complications of cirrhosis.

Key Barriers to the Provision and Utilization of Mental Health Services in Low-and Middle-Income Countries: A Scope Study.

Inadequate attention has been given to the provision of mental health (MH) services especially in low-and middle-income countries (LMICs). This study was aimed to identify key barriers to provide and utilize MH services in LMICs. A comprehensive search on7 important online databases was conducted for key barriers to the provision and utilization MH services in LMICs from Jan 2000 to Nov 2019. Five-step Arksey and O'Malley guideline was used for scope study. The extracted data were synthesized using a qualitative content analysis and thematic network. Three main themes identified as barriers to the provision of MH services in LMICs, namely resource and administrative barriers, information and knowledge barriers, as well as policy and legislation barriers. Also attitudinal barriers, structural barriers, knowledge barriers, and treatment-related barriers were four main themes emerged regarding the challenges of utilization of MH services. Equitable access to MH services in LMICs is influenced by many barriers in both provision and utilization sides. In order to alleviate these problems, health systems could adopt some strategies including integration of MH into the general health policy, improvement of public MH awareness, developing anti-stigma programs, reallocation of health resources toward high-priority MH needs, developing community-based insurance, as well as integration of MH services into all levels of health-care systems. The success of intervention strategies depends on the weight of these barriers in different socio-economic contexts.

Deriving the Turnover Frequency of Aminoxyl-Catalyzed Alcohol Oxidation by Chronoamperometry: An Introduction to Organic Electrocatalysis.

Organic electrosynthesis is an increasingly popular tool for driving and probing redox reactions. Recent advances in this field often employ an electrocatalyst to enhance the selectivity and efficiency of electrochemical reactions. A laboratory experiment was developed to introduce students to relevant mechanistic techniques in electrochemistry for analysis of electrocatalytic reactions using aminoxyl-catalyzed alcohol oxidation as a case study. This lab activity employs cyclic voltammetry for qualitative assessment of catalytic turnover prior to introducing students to chronoamperometry, an underutilized technique that facilitates quantitative determination of the rate of catalysis. Students identify and rationalize the important features of reversible electron transfer and a catalytic reaction in a cyclic voltammogram, probe the origin of scan rate effects on these traces, and calculate turnover frequency using a series of chronoamperograms. The method employs safe and readily available reagents: basic aqueous buffer solution, alcohol substrate, and an inexpensive organic aminoxyl catalyst. Student data presented herein were obtained from a course attended by undergraduate students, graduate students, and pharmaceutical chemists.

Tetramethylpiperidine N-Oxyl (TEMPO), Phthalimide N-Oxyl (PINO), and Related N-Oxyl Species: Electrochemical Properties and Their Use in Electrocatalytic Reactions.

N-Oxyl compounds represent a diverse group of reagents that find widespread use as catalysts for the selective oxidation of organic molecules in both laboratory and industrial applications. While turnover of N-oxyl catalysts in oxidation reactions may be accomplished with a variety of stoichiometric oxidants, N-oxyl reagents have also been extensively used as catalysts under electrochemical conditions in the absence of chemical oxidants. Several classes of N-oxyl compounds undergo facile redox reactions at electrode surfaces, enabling them to mediate a wide range of electrosynthetic reactions. Electrochemical studies also provide insights into the structural properties and mechanisms of chemical and electrochemical catalysis by N-oxyl compounds. This review provides a comprehensive survey of the electrochemical properties and electrocatalytic applications of aminoxyls, imidoxyls, and related reagents, of which the two prototypical and widely used examples are 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) and phthalimide N-oxyl (PINO).

Analyzing the interaction of main components of hidden curriculum in medical education using interpretive structural modeling method.

BACKGROUND: Hidden curriculum (HC) is considered as unintended learning experiences in medical education (ME). This may include values, norms, beliefs, skills, and knowledge which could potentially influence learning outcomes. HC has key components that must be identified and considered properly by individuals and organizations involved in ME. OBJECTIVES: This study aimed to determine the main components of hidden curriculum in medical education (HCME) and the interrelationships among them. METHODS: In this mixed-method study initially we performed a scoping review and determined the main components of HCME using qualitative content analysis approach. Then, the interrelationships among these components were investigated using Interpretive Structural Modeling (ISM). RESULTS: Ten key components for HCME were identified in scoping review. We classified them into four main categories including structural, educational, cultural, and social factors. The ISM analysis revealed that organizational rules and structure, dominant culture of educational environments, teaching and assessment approaches, as well as clinical and educational physical setting were the independent or driving factors. While, social components were dependent and influenced by basic components. CONCLUSION: The ISM model indicated that role modeling behaviors and interpersonal relationships (social factors) are under influence of underlying organizational and educational factors. These results should be considered at all stages of educational management including planning process, implementation of the programs, and development of formal curricula. According to the importance of contextual factors, components of HC must be analyzed and interpreted based on the specific conditions of each educational institution.