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Introduction: It has been extensively highlighted that SARS-CoV-2 affects the RAS (renin-angiotensin system) and the angiotensinconverting enzyme-2 receptors play the most important role in the presentation of the COVID-19 disease 2-5 The ACE2 is type I membrane protein expressed on endothelial cells in the kidney, heart, gastrointestinal tract, blood vessels, and, importantly, lung AT2 alveolar epithelial cells, which are particularly prone to SARS-CoV-2 infection As SARS-CoV-2 is a new coronavirus, and its cardiovascular complications and the underlying pathology is still emerging However, it is accepted that the virus affects the total vasculature in the human body and this infection becomes a highly accelerated process for the target organ damage In the case of acute cardiological manifestation, it is termed as Acute COVID-19 Cardiovascular Syndrome (ACovCS) by the American Heart Association's white paper 6 European Society of Cardiology (ESC) has published a detailed review paper 7 on the involvement of various cardiovascular target organs in COVID-19 disease This review clearly establishes a close two-way relationship between COVID-19 disease and all cardiovascular diseases (CVD) The prognosis is even worse in patients with preexisting cardiovascular system involvement Cardiovascular involvement in COVID-19 is seen as a key manifestation The best way to assess endothelial dysfunction is an assessment of its clinical manifestation, i e , an increase in arterial stiffness There have been multiple in vitro and in vivo studies that have shown that the vascular endothelium is an important factor in setting the vascular tone and endothelial dysfunction leads to arterial stiffness 8 Arterial stiffness and enhanced wave reflections are markers of cardiovascular disease and independent predictors of cardiovascular risk 9-12 Stiffening of the large arteries and enhanced wave reflections lead to increased left ventricular (LV) afterload, disturbed coronary perfusion, and mechanical fatigue of the arterial wall 13 The relationship between systemic inflammation and arterial stiffness is well established in the literature 14 The cause-and-effect relationship that acute systemic inflammation leads to deterioration of large-artery stiffness Findings in study15 on induced inflammation have shown that an acute inflammation caused a temporary increase in central blood pressure and arterial stiffness in terms of pulse wave velocity This implies the increased risk of cardiovascular events associated with acute systemic inflammation in the COVID-19 COVID-19 diseaserelated worldwide research and proposed mechanisms pointed to pathophysiological involvement of endothelial dysfunction and arterial wall compromise However, there was no empirical evidence of the functional compromise of arterial walls Hence, a study was urgently needed to study an increase in arterial stiffness in COVID-19 patients due to systemic inflammation to stratify the risk and mitigate further cardiovascular damage with guided therapeutic treatment based on the severity of arterial stiffness This pressing need is justified by a comprehensive review article16 published after the present study was envisaged We hope that the findings from our study will fulfill the need to a large extent Objectives: Primary objective: To study if the measurement of arterial stiffness using pulse wave velocity in mild-moderate and a severe group of COVID-19 patients can stratify cardiovascular risk Secondary objective: To determine if initial measurements and subsequent changes in arterial stiffness can project the future course of the COVID-19 patient and hence predict the grade of clinical management a confirmed COVID-19 patient would require Materials and methods: The present prospective nonrandomized observational study {titled - “To study the relationship of COVID-19 severity with arterial stiffness: A prospective cross-sectional study” (“COSEVAST study”)} was conducted in the COVID-19 ICU, medical ICU, and various wards of dedicated COVID hospital at AIIMS, Patna, Bihar, India The study protocol, informed consents, and other trial-related documents received the written approval of the Institutional Ethics Committee (IEC No AIIMS/Pat/IEC/2020/595) The study design was registered with the Clinical Trials Registry of India (CTRI No CTRI/2020/10/028489) All COVID-19 patients were subject to RT-PCR test and had a confirmed infection of the SARS-CoV-2 virus Participants, after understanding the study protocol and procedures, gave their written informed consent for the study The exclusion criteria were known history of any of these diseases - diabetes mellitus (DM), hypertension (HTN), CAD, stroke, neuropathy, PAD, nephropathy, MI, pregnancy, peripheral edema or inflammation, cardiac arrhythmia, and any preexisting cardiovascular disorder Patient categorization: The selected patients after fulfilling the inclusion criteria were grouped into three categories - mild, moderate, and severe category based on the latest NIH Guidelines 27 as follows: •Mild category: Individuals with mild signs and symptoms like fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell but who do not have shortness of breath, dyspnea, or abnormal chest imaging •Moderate category: Individuals who show evidence of lower respiratory disease during clinical assessment or imaging and who have a saturation of oxygen (SpO2) ≥ 94% on room air at sea level •Severe category: Individuals who have a saturation of oxygen (SpO2) 30 breaths/minute, PaO2/FiO2

Alkaline phosphatase (ALP) is an important biomarker to diagnose a number of diseases, such as anaemia, hepatobiliary diseases, chronic nephritis, and hypothyroidism. Therefore, the development of simple and convenient assays to monitor levels of ALP is highly desirable. In the present study, an aggregation-induced emission based simple, real-time, and direct fluorescence detection platform has been developed, by using a tetracationic pyridinium derivative of tetraphenylethylene (TPy-TPE) and anionic sodium hexametaphosphate (HMP) as component units. The sensing system, based on the TPy-TPE-HMP assembly, is highly responsive to the ALP dependent disintegration of the TPy-TPE-HMP aggregation complex, owing to HMP digestion by ALP. The sensing platform has an ALP detection limit of 16 mU mL

Sulfated cyclodextrins have recently emerged as potential candidates for producing host-induced guest aggregation with properties better than p-sulfonatocalixarenes that have previously shown numerous applications involving the phenomena of host-induced guest aggregation. In the class of sulfated cyclodextrins (SCD), sulfated β-cyclodextrin (β-SCD) remains the most extensively investigated host molecule. Although it is assumed that the host-induced guest aggregation is predominantly an outcome of interaction of the guest molecule with the charges on the exterior of SCD cavity, it has not been deciphered whether the variation in the cavity size will make a difference in the efficiency of host-induced guest-aggregation process. In this investigation, we present a systematic study of host-induced guest aggregation of a cationic molecular rotor dye, Thioflavin T (ThT) with three different sulfated cyclodextrin molecules, α-SCD, β-SCD and γ-SCD, which differ in their cavity size, using steady-state emission, ground-state absorption and time-resolved emission measurements. The obtained photophysical properties of ThT, upon interaction with different SCD molecules, indicate that the binding strength of ThT with different SCD molecules correlate with the cavity size of the host molecule, giving rise to the strongest complexation of ThT with the largest host molecule (γ-SCD). The binding affinity of ThT towards different host molecules has been supported by molecular docking calculations. The results obtained are further supported with the temperature and ionic strength dependent studies performed on the host-guest complex. Our results indicate that for host-induced guest aggregation, involving oppositely charged molecules, the size of the cavity also plays a crucial role beside the charge density on the exterior of host cavity.

Devising fluorescence-based turn-on probes for the specific and sensitive detection of Heparin is of utmost clinical importance. In this contribution, we have identified a molecular rotor based asymmetric cyanine probe, thiazole orange (TO), which enables an efficient colorimetric and fluorimetric detection of Heparin. TO undergoes the formation of emissive H-aggregates upon interaction with Heparin that display an impressive emission enhancement of ~22 fold together with drastic changes in the absorption spectra that yields a prominent colour change in the solution from orange to yellow. These seldom reported emissive H-aggregates of TO, serve as an efficient platform for Heparin detection with a LOD of 19 nM, fluorometrically and 34 nM, colorimetrically. The TO-Heparin complex is also accompanied by a large change in the excited-state lifetime. The TO-Heparin complex has been further utilized for the detection of Protamine, which is the only medically affirmed antitoxin of Heparin. Overall, our sensing system offers several advantages, such as, simple, dual read-out, economic and specific detection of Heparin with longer excitation and emission wavelength, rapid naked eye detection and utilizes an in-expensive commercially available fluoprophore, TO. Most importantly, our sensing system also displays a good performance in the biologically complex human serum matrix.

Control of fluorescent molecular assemblies is an exciting area of research with large potential for various important applications, such as, fluorescence sensing/probing, cell imaging and monitoring drug-delivery. In the present contribution, we have demonstrated control on the extent of aggregation of a dye-polyelectrolyte assembly using a macrocyclic host molecule, sulfobutylether-β-cyclodextrin (SBE-β-CD). Initially, a cationic molecular rotor based organic dye, Auramine-O (AuO), undergoes aggregation in the presence of an anionic polyelectrolyte, polystyrene sulfonate (PSS), and displays a broad intense new emission band along with large variation in its absorption features and excited-state lifetime. A manipulation of the monomer-aggregate equilibrium of the dye-polyelectrolyte assembly has been achieved by introducing a cyclodextrin based supramolecular host, SBE-β-CD, which leads to relocation of AuO molecules from polyelectrolyte (PSS) to supramolecular host cavity, owing to the formation of a host-guest complex between AuO and SBE-β-CD. A reversible control on this manipulation of monomer-aggregate equilibrium is further achieved by introducing a competitive guest for the host cavity i. e., 1-Adamantanol. Thus, we have demonstrated an interesting control on the dye-polyelectrolyte aggregate assembly using a supramolecular host molecule which open up exciting possibilities to construct responsive materials using a repertoire of various host-specific guest molecules.

The field experiments were conducted at Student’s Instruction Form, ANDUA&T, Kumarganj Ayodhya. The climate is hot and humid summer and cold winters, during the rabi crop season in the year 2017-18. One hundred genotypes of Rapeseed-mustard were used for the present investigation. The earliest appearance of disease (30 days) was noted in genotypes RAURD-09-32, RM-WR-09-5, PAB-09-07, PRB-2004-3-4, RGN-307, RH-0834, RH-0902, RH-0952, RH-0903, RHH-1101, YSWB- 2012/9 (44 days) PPBJ-2, RAURD-09-78, and (45 days) PPBN-3, PT-2006-4 and lowest disease severity was recorded genotypes PHR-2, (9.5) PAB- 2004-4 (20.5) PPBJ-2 (22.2), PPBN-3 (22.3) PPBN-2 (22.6) PPBJ-5 (23.3), PPBJ-3 (24.3), PPBJ-4 (24.5) PAB-2005-16 (24.5), RRM-789, (43.6), RH-0555A, (43.7). AUDPC showed more susceptible genotypes the lowest PHR-2 (214.5) was recorded and genotypes screened, none of the genotypes were found disease -free or highly resistance, only 1 genotype namely (PHR-2) were found resistance, 8 genotypes namely (PPBN-2, PPBN-3, PPBJ-3, PPBJ-2, PPBJ-5, PPBJ-4, PAB-2005-16, PAB- 2004-4), were rated as moderated resistance, 37 moderated susceptible and 54 as susceptible.

The aggregation of small molecules in aqueous solution is known to be influenced by the ionic strength of the medium; however, the role played by the identity of salt in the phenomenon of small molecule aggregation is rarely investigated. In the present contribution, we have investigated the effect of counter-anions on the aggregation of a popular cationic amyloid sensing probe, Thioflavin-T (ThT), by taking six different anions, viz. chloride, bromide, acetate, iodide, tetrafluoroborate, and perchlorate. Our results clearly indicate that it is not the ionic strength of the medium which solely controls aggregation of small molecules but distinct ions behave distinctly with regard to the organization. In fact, distinct ion effects play a major role in the salt induced organization of fluorophores. Using detailed steady-state emission, time-resolved emission, and ground-state absorption measurements, the optical properties of salt induced aggregates of ThT have been characterized. We have rationalized our observations on the basis of the theory of matching water affinity, which suggests that the matching free hydration energy is a critical aspect for the formation of contact ion pairs, which eventually results in aggregation. In brief, a larger sized anion, perchlorate, has a lower free energy of hydration and forms a suitable contact ion pair, with a larger organic cation, ThT, having weaker hydration. This contact ion-pair formation subsequently leads to the formation of an aggregate assembly which is found to be emissive in nature. Therefore, it is possible to induce aggregation of ThT by selecting the right counterion with the appropriate size, which may help us to evaluate the false positive signals when high ionic strength and specific counterions are present in the sensing matrix.

Tunable and controllable emission is an extremely desirable feature for advanced functional materials that finds usage in optoelectronic utilization, fluorescence probing/sensing, drug-delivery monitoring, etc. In the present contribution, we have employed a macrocyclic host molecule, sulfobutyl ether-β-cyclodextrin (SBE-β-CD), as a tuning agent for an intensely emissive aggregate assembly of a molecular rotor dye, thioflavin-T (ThT), in the presence of an anionic polyelectrolyte, polystyrene sulfonate (PSS). The macrocyclic host breaks the PSS templated ThT aggregates and leads to encapsulation of released ThT molecules, tailoring the emission response of the system in terms of intensity and wavelength. Utilizing the established selectivity of the cyclodextrin-adamantane system, reverse control of this tunable emission has been further achieved. The controllable fluorescence system has been extensively investigated using ground-state absorption, steady-state and time-resolved emission spectroscopy. This kind of supramolecular tailoring of self-assembled aggregate emission has enormous potential in the field of fluorescence sensors and probes, and imaging and tracking in biological systems.

Thrombin is an important enzyme that plays a pivotal role in the blood clotting pathways. An imbalance in the activity of this enzyme is clinically known to be associated with various diseases, such as thrombosis, inflammation, atherosclerosis, and haemophilia, suggesting the need to devise sensors for Thrombin detection. However, the majority of the fluorescence-based Thrombin assays rely on fluorescence labelling assays or Thrombin specific recognition biomolecules, such as, aptamers or antibody which requires sophisticated techniques and makes it very expensive. Herein, we report a simple, selective, sensitive and label-free fluorescence detection scheme for Thrombin which is based on the interaction between Thrombin and a fluorescent complex of Heparin with a molecular rotor dye, Thioflavin-T. The detection scheme exploits selective interaction between cationic Thrombin and anionic Heparin to modulate the monomer-aggregate equilibrium of the Thioflavin-T-Heparin system. Importantly, the present system offers a ratiometric response that has the ability for robust quantification of Thrombin concentration even in complex medium. The involvement of all commercially available components is a crucial advantage of this detection scheme. Further, the detection scheme also shows reasonable response in diluted serum matrix.

Protamine, a polycation, is biologically and medically relevant protein. Protamine exhibits a wide array of functions in biological processes like gene transfer, tissue and organogenesis, cell reproduction, etc. Medically, Protamine is the only clinically approved antidote for Heparin and is routinely used in various surgical interventions, and hence controlling Protamine dosing in patients is very crucial. Taking into account the medical significance of Protamine, designing simple, reliable and sensitive fluorescence sensors is highly desirable. In this work, we propose one such sensitive and reliable fluorescent sensor which is based on a template of dye-polyelectrolyte assembly constituting a molecular rotor dye, Thioflavin-T and an anionic synthetic polyelectrolyte, polystyrene sulfonate. The addition of Protamine, prompts drastic modulations in spectral features of dye-polyelectrolyte assembly which enables sensitive detection of Protamine in aqueous solution. Apart from sensitive detection, our sensing platform aids in highly selective sensing of Protamine compared to other proteins. Moreover, our sensor system is constructed on label-free, inexpensive, commercially available molecules posing as an advantage over other sensor systems which involve laborious synthesis protocols. Most importantly, our sensor template is able to sense Protamine in diluted serum sample, indicating the potential practical utility of our sensor system.

Trypsin, a pancreatic serine protease, due to its narrow specificity and selectivity, has been tremendously used in food technology, proteome analysis, modulating soy protein allergenicity, antihypertensive peptide production, as well as, a biomarker in diseases such as pancreatitis, cystic fibrosis

Although cyclodextrins have been extensively utilized in various branches of supramolecular chemistry due to their numerous attractive attributes, however, to achieve even advanced applications, they often need structural modification through substitutions of suitable functional groups at their rims. A systematic investigation on how the degree of substitution on the cyclodextrin rims affects the binding affinity for a given guest molecule has however rarely been reported, especially from the perspective of photophysical studies. Herein, we report the non-covalent interaction of a styryl based dye, LDS-798, with three different sulfobutylether beta cyclodextrin (SBEnβCD) derivatives bearing varying degrees of substitution (n), using ground state absorption, steady-state emission, excited-state lifetime and time-resolved fluorescence anisotropy measurements. The dye–host binding constant values indicate that the strength of the interaction between LDS-798 and SBEnβCD derivatives follows an increasing trend with an increasing number of tethered sulfobutylether substituents on the cyclodextrin rims, which is attributed to the gradual increase of the electrostatic interaction between the negatively charged sulfobutylether groups and the positively charged LDS-798. Excited state lifetime measurements and ionic strength dependent studies on the dye–SBEnβCD complexes further support the increased affinity between the dye and the host in the supramolecular complexes, with an increasing number of sulfobutylether substituents on the βCD rims. The obtained results suggest that the molecular recognition of LDS-798 with SBEnβCD derivatives can be tuned very effectively by varying the number of sulfobutylether substituents on the cyclodextrin rims. Considering that SBE7βCD is one of the FDA approved agents for drug formulations, the obtained results with other SBEnβCD hosts may be useful in designing selective drug delivery applications, drug formulations, and effective fluorescence on–off switches.

Considering the biological relevance of adenosine triphosphate (ATP) as an "energy currency" in all organisms and significance of its detection in various diseased conditions, enormous efforts have been made to develop selective and sensitive fluorescent sensors for the detection of ATP. However, these developed sensor probes frequently involve technically challenging and time-consuming synthetic protocols for the production of sensor molecules and often suffer from poor solubility in aqueous medium. Another major disadvantage of these developed sensor systems is their single wavelength based operation which makes their performance susceptible to minute changes in experimental conditions. Herein, we report a fluorescence turn-on ratiometric sensor for the detection of ATP which operates by the dissociation of Thioflavin-T-sulphated-β-cyclodextrin supramolecular assembly by Zn2+ followed by ATP induced reassociation of the same. This modulation of the monomer/aggregate equilibrium of the supramolecular assembly followed by subsequent interactions with Zn2+ and ATP acts as an optimal scheme for the ratiometric detection of ATP. Overall this supramolecular ensemble based sensing platform provides a simple, sensitive, selective and label free detection approach for ATP in aqueous solution. Importantly, our sensor platform responds to ATP in the biologically complex media of serum samples suggesting its potential for possible applications in real-life scenarios.

The combination of supramolecular chemistry and aggregation-induced emission-based luminogens (AIEgens) has recently attracted tremendous attention because of its ability to offer large emission enhancement even in substantially dilute solutions. In this work, a new aggregation-induced emission (AIE)-based supramolecular assembly has been reported, which consists of a polyanionic cyclodextrin derivative and a tetracationic tetraphenylethylene (TPE) derivative. Ionic cyclodextrins have attracted significant attention in host-guest supramolecular chemistry and pharmaceutical industry. However, ionic derivatives of β-cyclodextrins have not been explored to establish noncovalent interactions-based aggregation assembly of the most popular class of AIEgens, i.e., tetraphenylethylene derivatives. The current report demonstrates AIE of a tetracationic methyl pyridinium derivative of tetraphenylethylene (TPy-TPE) induced by a polyanionic sulfated β-cyclodextrin (S-βCD). The AIE-based supramolecular assembly has been thoroughly investigated using steady-state fluorescence, ground-state absorbance, and time-resolved fluorescence measurements. Further, the response of the supramolecular assembly towards external stimuli, such as, ionic strength, pH, and temperature, has been investigated. In addition, the complexation behavior of the TPE derivative has also been compared with the native neutral β-cyclodextrin derivative, which delineates the important role of the negatively charged portal of S-βCD in inducing aggregation of the TPy-TPE. The stoichiometry of the complex has been found to be 3:1 for TPy-TPE:S-βCD, using Job's plot analysis. Finally, to get insights into the underlying interactions between the supramolecular assembly components, molecular docking calculations have been performed.

Oxygen supplementation is required for approximately 14% of the patients diagnosed of having COVID-19 infection. Despite the use of conventional oxygen therapy, 5% among these require treatment in the intensive care unit (ICU). Here, we are describing a situation in which oxygen therapy was delivered to the patients by making an assembly of oxygen tubing, three-way stopcock, and high-flow nasal cannula (HFNC) present in the hospital setting following the malfunction of air blender of HFNC machine (Fig. 1). This assembly might be useful as rescue oxygen therapy during a malfunction of HFNC machine and in resource-limited settings where HFNC machine is not available. The mechanisms of action could be (1) washout of anatomic dead space due to medium oxygen flow, (2) improved gas mixing in large airways, and (3) increased oxygen concentration inside the conducting airway. How to cite this article: Kumar A, Kumar A, Kumar N, Kumar A, Singh V, Kumar S, et al. Repackaging of Malfunctioning High-flow Nasal Cannula as a Rescue Oxygen Therapy: An Innovation amid COVID-19 Crisis. Indian J Crit Care Med 2021;25(8):948–949.

The change in the color of chromophore upon being embedded in a biological tissue is known as metachromasia. Basic Orange 21 (BO21) is a cationic polymethine dye that has been implied as a supravital dye, which produces metachromasia in leukocytes. An improved differential counting of leukocytes has been achieved in the clinical setup based on characteristic metachromatic expressions of BO21 for different types of leukocytes. Although BO21 has been utilized as a chromatic indicator for leukocyte counting, there are limited number of investigations that focus on the factors that may be responsible for the spectral shift in absorption and emission spectra of BO21, which leads to its metachromatic behavior. In this work, we have investigated the effect of a synthetic anionic polyelectrolyte, polystyrene sulfonate (PSS), on the photophysical properties of BO21, using steady-state emission, ground-state absorption, and time-resolved emission measurements, to get an understanding of the factors that may be responsible for the spectral shift of BO21 in the cellular environment. PSS induces aggregation of BO21 molecules with large changes in its photophysical properties; this appears to be most likely the mechanism of spectral shift for BO21 reported in the cellular environment. The employment of external stimulus reveals BO21 aggregates to be significantly responsive toward external stimuli, for example, temperature and presence of salt in the medium, which further strengthens the proposal of aggregate formation. Further, we have also employed fluorescence upconversion spectroscopy with subpicosecond time resolution to estimate the excited-state lifetime of BO21.

Non-covalent interactions of different dyes/drugs with various biological agents, which lead to large modulations in photophysical properties, have attracted attention of many scientists over the decades due to their versatile applicability in different fields. Herein, we report the spectroscopic investigation of non-covalent interaction of a synthesized BODIPY-benzimidazole conjugate (BDZ) dye with bovine serum albumin (BSA), which results in distinctive modulations in the photophysical properties of the dye. The structural immobilization, and reduced propensity of forming the weakly emissive intramolecular charge transfer (ICT) state of the dye, inside the confined BSA cavity, results into a significant increase in fluorescence intensity, which is also supported by the increase in the excited-state lifetime and fluorescence anisotropy decay time of the dye. Molecular docking calculations and competitive binding experiments reveal that the BDZ dye binds selectively to site IB with a reasonably high binding constant Kb ˜ 1.38 × 104 M−1. The BDZ-BSA complex shows a notable decrease in fluorescence intensity in the presence of guanidinium hydrochloride, indicating the selective binding of the dye with the native form of the BSA protein as compared to its denatured form. Formation of BDZ-BSA complex, which emits in the biologically favorable red region, makes the studied system a probable choice to monitor the denatured form of the BSA protein, biological sensing study, and to understand the transport mechanism of similar kind of drugs and other metabolites with serum albumin protein.

Fluorescent sensor for the perrhenate/pertechnetate anions in aqueous media are rarely reported in literature as their large size and low charge density poses great challenge to their detection. Herein, we report the first fluorescent turn-on ratiometric sensor for perrhenate anion, exploiting its weak hydration property which leads to an advantageous formation of a contact ion-pair of perrhenate anion with a well-known cationic ultrafast molecular rotor dye, Auramine O. This ion-pair formation, in turn, leads to a fluorescent aggregate assembly that provides an excellent opportunity to detect perrhenate anion in aqueous solution.