Mitochondria-Directing Fluorogenic Probe: An Efficient Amyloid Marker for Imaging Lipid Metabolite-Induced Protein Aggregation in Live Cells and Caenorhabditis elegans.

The design and development of optical probes for sensing neurotoxic amyloid fibrils are active and important areas of research and are undergoing continuous advancements. In this paper, we have synthesized a red emissive styryl chromone-based fluorophore (SC1) for fluorescence-based detection of amyloid fibrils. SC1 records exceptional modulation in its photophysical properties in the presence of amyloid fibrils, which has been attributed to the extreme sensitivity of its photophysical properties toward the immediate microenvironment of the probe in the fibrillar matrix. SC1 also shows very high selectivity toward the amyloid-aggregated form of the protein as compared to its native form. The probe is also able to monitor the kinetic progression of the fibrillation process, with comparable efficiency as that of the most popular amyloid probe, Thioflavin-T. Moreover, the performance of SC1 is least sensitive to the ionic strength of the medium, which is an advantage over Thioflavin-T. In addition, the molecular level interaction forces between the probe and the fibrillar matrix have been interrogated by molecular docking calculations which suggest the binding of the probe to the exterior channel of the fibrils. The probe has also been demonstrated to sense protein aggregates from the Aß-40 protein, which is known to be responsible for Alzheimer's disease. Moreover, SC1 exhibited excellent biocompatibility and exclusive accumulation at mitochondria which allowed us to successfully demonstrate the applicability of this probe to detect mitochondrial-aggregated protein induced by an oxidative stress indicator molecule 4-hydroxy-2-nonenal (4-HNE) in A549 cell lines as well as in a simple animal model like Caenorhabditis elegans. Overall, the styryl chromone-based probe presents a potentially exciting alternative for the sensing of neurotoxic protein aggregation species both in vitro as well as in vivo.

Guest Binding with Sulfated Cyclodextrins: Does the Size of Cavity Matter?

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 ß-cyclodextrin (ß-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, ß-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.

Thioflavin-T-Incorporated Cerium-ATP Coordination Polymer Nanoparticles: A Promising System for Detection of Uranyl Ion (UO22+) in Aqueous Medium.

Lanthanide-based coordination polymer nanoparticles (Ln-CPNs) are studied for analytical and biomedical sensing, mainly utilizing the luminescent properties of lanthanides. However, the inclusion of fluorescent guest molecules within the nanoparticles can lead to a stimuli-responsive system with modulated photo-physical properties that can be useful for detecting analytes. In this work, we have synthesized cerium(III) coordination polymer nanoparticles using adenosine triphosphate (ATP) molecules as the ligands. The porous polymeric structure enables CPNs for reversible inclusion and release of thioflavin-T (ThT), which is a weakly emissive dye in the free state but becomes highly emissive when incorporated into the Ce-ATP CPNs. Modulation of the photo-physical properties of ThT-incorporated CPNs in response to the radiotoxic and environmentally alarming uranyl ion (UO22+) has been used for its detection in aqueous medium in the range of 0-20 µM by fluorimetry with an LOD of 80 ng mL-1 (0.34 µM) in deionized water without interference from the most commonly occurring metal ions. Furthermore, the sensing platform has been successfully utilized for UO22+ determination in seawater sample without any pre-treatment and adjustment of pH.

Methods of Determining Irritable Bowel Syndrome and Efficiency of Probiotics in Treatment: A Review.

Background: Irritable bowel syndrome (IBS) is a prevalent lifestyle-associated ailment linked to the gut microbiota that significantly influences patients' quality of life. A notable correlation exists between Blastocystis infections and susceptibility to IBS, with infected individuals exhibiting an increased likelihood of developing the condition. Despite promising results from using probiotics to modulate the gut microbiota and manage IBS, the precise mechanisms and potential risks remain unclear. Objective: This review aims to explore the therapeutic potential of probiotics, particularly Saccharomyces boulardii, in the management of IBS, highlighting the role of the gut microbiota and the gut-brain axis in IBS pathophysiology. Methods: A comprehensive literature survey was conducted to examine the association between gut microbiota and IBS, the role of probiotics in managing IBS, the mechanisms of their action, and the potential risks associated with their long-term use. Additionally, this study addresses the influence of Blastocystis infections on IBS susceptibility and evaluates various ongoing clinical trials investigating probiotic use for IBS. Results: S boulardii, a yeast species with probiotic properties, has demonstrated effectiveness in both the treatment and prophylaxis of IBS. Its administration is associated with a decrease in the proinflammatory cytokine interleukin 8 and an increase in the anti-inflammatory cytokine interleukin 10. Probiotics appear to function by inhibiting the growth of pathogenic microorganisms and regulating neurotransmitter activity, influencing the gut-brain axis. However, selecting appropriate probiotic strains and dosing regimens is crucial because of potential adverse effects, such as infections and allergic reactions. Conclusions: Probiotics, specifically S boulardii, offer a promising avenue for IBS management by modulating gut microbiota. However, further research is necessary to delineate the precise mechanisms of action, optimal strains, dosing regimens for IBS treatment, and potential risks associated with long-term use. A comprehensive approach incorporating probiotics, a low-FODMAP diet, and cognitive-behavioral therapy may provide effective management of IBS symptoms.

A cationic AIEgen and hexametaphosphate based simple and convenient fluorometric assay for alkaline phosphatase and its inhibitor.

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-1 and linear range of 0-742 mU mL-1, respectively. The enzyme kinetic parameters, Km and Vmax, have been evaluated. In addition, the potential applicability of the TPy-TPE-HMP sensing system has also been shown with diluted human serum samples. Moreover, the TPy-TPE-HMP probe system is also useful for screening inhibitors of ALP.

Supramolecular Control on the Optical Properties of a Dye-Polyelectrolyte Assembly.

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-ß-cyclodextrin (SBE-ß-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-ß-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-ß-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.

Effect of counter-anions on the aggregation of Thioflavin-T.

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.

Supramolecular tuning of thioflavin-T aggregation hosted by polystyrene sulfonate.

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-ß-cyclodextrin (SBE-ß-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.

Gargling with 7.5% Sodium Bicarbonate Solution for SARS-CoV-2 Viremia Clearance: Our Institutional Clinical Experience.

BACKGROUND: Gargling had been reported to have some roles in the prevention and treatment of respiratory tract infections. The purpose of this study was to assess the ability of regular gargling using 7.5% sodium bicarbonate to eliminate SARS-CoV-2 in the oropharynx and nasopharynx. MATERIALS AND METHODS: This pilot, open-labeled, nonrandomized, parallel single-center study. The effect of 30 seconds, three times per day gargling using 7.5% sodium bicarbonate solution-25 mL on SARS-CoV-2 viral clearance among coronavirus disease-2019 (COVID-19) patients in a dedicated COVID hospital at All India Institute of Medical Sciences, Patna, Bihar, India. We monitored the progress on by days 0, 1, 2, 3, 4, 5, 6, and 7 by observing variables like clinical category, P/F ratio, neutrophil/lymphocyte ratio (NLR) ratio, platelet count, ferritin, lactate dehydrogenase (LDH), CRP, procalcitonin, d-dimer, INR, APTT, and sequential organ function assessment (SOFA) score. We have also done repeat reverse transcription-polymerase chain reaction (RT-PCR) testing on day 5 and day 7. RESULTS: A total of 10 patients (7 males and 3 females) were included in our study after confirmed COVID positivity. The age range was from 30 to 61 years. Based on clinical severity and P/F ratio, 7 patients were included in the milder group as their ratio was more than 200 and the rest 3 patients were included in the moderate group as P/F ratio was less than 200. Two respondents had comorbidities, which were non-Hodgkin's lymphoma and ovarian carcinoma. Viral clearance was achieved at day 7 in 3 of 10 patients. However, the analysis of using 7.5% sodium bicarbonate 25 mL gargle statistically showed nonsignificant p-value for all of our studied variables. However, the PCR results were negative on 24 hours apart, i.e., on day 5 and day 7. CONCLUSIONS: This is only a preliminary study which showed that gargling with 7.5% sodium bicarbonate may not be effective in achieving early SARS-CoV-2 viral clearance among mild COVID-19 patients. However, still larger studies are required to ascertain the benefit of gargling for different stages of COVID-19 patients with keeping in mind the important variables suggestive of viremia clearance. HOW TO CITE THIS ARTICLE: Kumar N, Kumar A, Mahto M, Singh PK. Gargling with 7.5% Sodium Bicarbonate Solution for SARS-CoV-2 Viremia Clearance: Our Institutional Clinical Experience. Indian J Crit Care Med 2021;25(7):791-794.

Repackaging of Malfunctioning High-flow Nasal Cannula as a Rescue Oxygen Therapy: An Innovation amid COVID-19 Crisis.

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.

Dual Oxygen Therapy in COVID-19 Patient: A Method to Improve Oxygenation.

Approximately 5-6% of patients diagnosed to have COVID-19 infection present with severe hypoxemia requiring invasive ventilation or non-invasive ventilation (NIV). Additional oxygen to patients on NIV can be given by nasal prong or by connecting oxygen tubing directly to the O2 pick-off port of the NIV mask or by connecting oxygen tubing to the single-limb circuit in between ventilator and patient. Dual oxygen therapy improves oxygenation in COVID-19 patients on NIV. This method may make the patient more comfortable, increase tolerance to NIV, increase the usefulness of NIV for moderate and severe COVID-19 acute respiratory distress syndrome (ARDS). How to cite this article: Kumar A, Kumar A, Sinha C, Kumar N, Singh K, Singh PK. Dual Oxygen Therapy in COVID-19 Patient: A Method to Improve Oxygenation. Indian J Crit Care Med 2021;25(2):231-233.

Acute Exacerbation of Cough as a Precipitating Cause of Hypoxia in COVID-19 Patients.

Kumar A, Kumar A, Kumar A, Sinha C, Kumar N, Singh PK. Acute Exacerbation of Cough as a Precipitating Cause of Hypoxia in COVID-19 Patients. Indian J Crit Care Med 2021;25(11):1324-1325.

Off-label Use of Itolizumab in Patients with COVID-19 ARDS: Our Clinical Experience in a Dedicated COVID Center.

Severe acute respiratory syndrome coronavirus 2 has affected millions of people worldwide. This pandemic requires newer medical management strategies to control the morbidity and mortality associated with the disease. Several approaches, including global targeting of inflammation or neutralizing a single key inflammatory mediator, are being employed to cope with cytokine storms in coronavirus disease-2019 (COVID-19). The role of anti-inflammatory biologics, such as acalabrutinib, tocilizumab, anakinra, and itolizumab can become relevant. Itolizumab is a humanized recombinant immunoglobulin G1 monoclonal antibody. It targets the extracellular, scavenger receptor cysteine-rich (SRCR) distal domain 1 of CD6 and is responsible for priming, activation, and differentiation of T-cells. Itolizumab has been approved by the Drug Controller General of India for the treatment of COVID-19 in India. Here, we shared our clinical experience of 20 patients having moderate acute respiratory distress syndrome (ARDS) due to COVID-19 on treatment with itolizumab. We observed the mortality benefit with single-dose itolizumab (1.6 mg/kg) in patients having moderate COVID-19 ARDS. HOW TO CITE THIS ARTICLE: Kumari P, Kumar A, Sinha C, Kumar A, Singh PK, Arun SK. Off-label Use of Itolizumab in Patients with COVID-19 ARDS: Our Clinical Experience in a Dedicated COVID Center. Indian J Crit Care Med 2021;25(4):467-469.

The COSEVAST Study Outcome: Evidence of COVID-19 Severity Proportionate to Surge in Arterial Stiffness.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the cardiovascular system at many levels. It initially infects endothelial cells, inducing marked endothelial damage and inflammation. However, there was no empirical evidence of functional compromise of arterial walls. AIMS AND OBJECTIVE: Our primary objective was to study functional arterial damage in coronavirus disease 2019 (COVID-19) and establish the noninvasive measurement of arterial stiffness as an independent marker of disease severity. MATERIALS AND METHODS: We recorded the arterial stiffness of 23 mild, 21 moderate, and 20 severe COVID-19 patients grouped on the latest National Institute of Health (NIH) severity criteria. We observed arterial stiffness of COVID-19 patients with standard parameters like noninvasive estimated carotid-femoral pulse wave velocity (cfPWV), age-normalized increase in cfPWV (ANI_cfPWV), age-normalized increase in aortic augmentation pressure (ANI_AugP), and heart rate-normalized augmentation index (HRN_ AIx). All the parameters were also corrected for statistically significant confounding factors. RESULTS: Moderate and severe COVID-19 patients have extremely significantly elevated arterial stiffness than mild patients. In mild patients, cfPWV (829.1 ± 139.2 cm/second) was significantly lower than both moderate (1067 ± 152.5 cm/second, p <0.0001) and severe (1416 ± 253.9 cm/second, p <0.0001) patients. ANI_cfPWV in moderate and severe patients was significantly higher than mild patients (mild: 101.2 ± 126.1 cm/second; moderate: 279 ± 114.4 cm/second; severe: 580.1 ± 216.4 cm/second; intergroup p <0.0001). The results even after correction for significant confounding factors did not show any considerable change in the increasing trend of arterial stiffness. CONCLUSION: This study establishes the functional deterioration of arteries in proportion to the severity of COVID-19. HOW TO CITE THIS ARTICLE: Kumar N, Kumar S, Kumar A, Bhushan D, Kumar A, Kumar A, et al. The COSEVAST Study Outcome: Evidence of COVID-19 Severity Proportionate to Surge in Arterial Stiffness. Indian J Crit Care Med 2021;25(10):1113-1119.

Does the degree of substitution on the cyclodextrin hosts impact their affinity towards guest binding?

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 (SBEnßCD) 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 SBEnßCD 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-SBEnßCD 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 ßCD rims. The obtained results suggest that the molecular recognition of LDS-798 with SBEnßCD derivatives can be tuned very effectively by varying the number of sulfobutylether substituents on the cyclodextrin rims. Considering that SBE7ßCD is one of the FDA approved agents for drug formulations, the obtained results with other SBEnßCD hosts may be useful in designing selective drug delivery applications, drug formulations, and effective fluorescence on-off switches.

An ATP responsive fluorescent supramolecular assembly based on a polyelectrolyte and an AIE active tetraphenylethylene derivative.

Aggregation induced emission (AIE) active probes have attracted enormous attention due to their wide-spread and ever increasing number of applications in the sensing of chemically and biologically important molecules. AIE probes undergo drastic modulation in their photophysical features from a monomeric to aggregated state. In the current work, we report the aggregation of tetra-anionic Su-TPE (AIE active probe) in the presence of a cationic polyelectrolyte, poly(allylaminehydrochloride) (PAH). A supramolecular assembly is formed by the electrostatic interaction between cationic PAH and anionic Su-TPE molecules, which leads to drastic modulations in the spectral features of anionic Su-TPE upon addition of cationic PAH. The Su-TPE-PAH aggregate assembly has been investigated using various photophysical techniques, such as, ground-state absorption, steady-state and time-resolved emission spectroscopic techniques along with 1H NMR measurements. The Su-TPE-PAH aggregate assembly is found to be responsive towards the ionic strength of the medium and temperature which results in drastic modulations of the spectral features of the emissive supramolecular aggregate assembly. Finally, the specific recognition of an important bioanalyte, ATP, has been achieved using the formed Su-TPE-PAH supramolecular aggregate assembly as a sensing platform which displays good selectivity and high sensitivity towards ATP. Importantly, the developed sensor platform could also function in the human serum matrix, hence, demonstrating the potential of the established sensor platform for real-life applications in near future.

Enzyme-based optical biosensors for organophosphate class of pesticide detection.

Organophosphorus pesticides, widely used as insecticides for crop protection, are classified as an extremely toxic class of chemical compounds by the World Health Organization (WHO). Organophosphorus pesticides show marked specificity for the enzyme acetylcholinesterase, and can cause irreversible harm to the nervous system. The excessive use of organophosphorus pesticides, specifically in developing countries, made WHO to impose a ban on certain organophosphorus pesticides being sold to the developing nations. WHO and the Food and Agriculture Organization of United Nations, in joint meetings on pesticide residues, have stressed the need to develop easy, rapid, and sensitive methods to detect the presence of organophosphorus pesticides in food and water. In this regard, a number of review articles have been published explaining a myriad of detection methods for organophosphorus pesticides. Among these, optical detection methods, using biological molecules as the recognition element, provide a number of advantages, such as, high sensitivity and selectivity, simple operation, fast response and cheap instrumentation, and can really prove to be an effective alternative to the time-consuming traditional methods in the current scenario. Therefore, in this review article, we have discussed the recent advances in the field of biosensors employing the optical detection of organophosphorus pesticides. Specifically, various biosensors developed, using enzymes acetylcholinesterase and organophosphate hydrolase, have been categorized on the basis of the material used for their fabrication. A systematic discussion of the working principles, analytical parameters, and advantages and disadvantages of the various biosensors, has been attempted, along with a future perspective, on the challenges and possible improvements in the field of optical detection of organophosphorus pesticides.

A novel supramolecule-based fluorescence turn-on and ratiometric sensor for highly selective detection of glutathione over cystein and homocystein.

A cyclodextrin-based fluorescence light-up and ratiometric sensor is reported for highly selective and sensitive recognition of glutathione over cystein and homocystein. The sensing scheme developed builds up on a supramolecular assembly formed between a molecular rotor dye (ThT) and a polyanionic supramolecular host (sulfated-ß-cyclodextrin, SCD). The detection scheme is accomplished as follows: firstly, the bivalent Cu2+ quenches the emission from ThT-SCD assembly by causing the dissociation of ThT molecules from SCD surface. Secondly, when GSH is added to the copper-quenched system, owing to specific interaction between Cu2+ and GSH, Cu2+ is removed from the SCD which again allows the formation of ThT-SCD assembly. Indeed, this scheme of disassembly and reassembly successively caused by Cu2+ and GSH in the aqueous solution empowers our sensor framework to work as a good ratiometric sensor for the detection of GSH. The sensor scheme shows a linear response in the range 0-250 µM with a LOD of 2.4 ± 0.2 µM in aqueous solution and 13.6 ± 0.5 µM in diluted human serum sample. The sensor system is excited at 410 nm and the emission signal is plotted as a ratio of intensity at 545 nm (aggregate band) and 490 nm (monomer band). This ratiometric sensor system is highly selective to glutathione over cystein, homocystein, and other amino acids. Additionally, response of the sensor system towards GSH in complex biological media of serum samples demonstrates its potential for practical utility. Graphical abstract.

Impact of Critical Illness on Quality of Life after Intensive Care Unit Discharge.

OBJECTIVE: To assess the quality of life (QoL) following intensive care unit (ICU) discharge using 6 months' prospective follow-up and to analyze the risk factors affecting quality-of-life post-discharge. DESIGN: A prospective observational cohort study. Conducted on adult patients, discharged from ICU after more than 7 days' stay. Study duration is from January 2017 to October 2018. Patients <18 years, nonconsenting, preexisting neurological illness, and lost to follow-up were excluded. Follow-up was done at 1 and 6 months using the SF-36 questionnaire. The pre-ICU functional status, patient demographics, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, New York Health Evaluation (NYHA) classification, and details of ICU stay were collected. RESULTS: One hundred patients (M = 60, F = 40) with ICU stay (13.64 ± 3.75 days), days of mechanical ventilation (7.93 ± 3.89 days), admission APACHE II (18.88 ± 4.34) and SOFA (7.73 ± 1.54) scores. Comparison showed physical component summary (PCS) score and mental component summary (MCS) score at pre-ICU were 55.12 and 55.09 which decreased to 39.59 and 35.49 (p < 0.05) at 1 month post-discharge and 47.93 and 37.46 at 6 months. Age, APACHE II, and SOFA scores are the significant factors affecting PCS and MCS. Length of ICU stay and duration of mechanical ventilation did not affect significantly at 6 months. When compared with general population PCS and MCS showed significant deterioration at 1 and 6 months. CONCLUSION: Post-ICU discharge patients have significant functional impairment and compromised health-related QoL (HRQoL). Age and severity of illness significantly affects health quality parameters and decline is below the normal data of general population. HOW TO CITE THIS ARTICLE: Rai R, Singh R, Azim A, et al. Impact of Critical Illness on Quality of Life after Intensive Care Unit Discharge. Indian J Crit Care Med 2020;24(5):299-306.

An Ultrafast Molecular-Rotor-Based Fluorescent Turn-On Sensor for the Perrhenate Anion in Aqueous Solution.

Devising sensors for the perrhenate anion in aqueous media is extremely challenging, and has seldom been reported in the literature. Herein, we report a fluorescence turn-on sensor for the perrhenate anion in aqueous media based on the aggregation-induced emission of a popular ultrafast molecular rotor dye, Thioflavin-T. The selective response towards the perrhenate anion has been rationalized in terms of matching water affinity, with the weakly hydrated perrhenate anion spontaneously forming a contact ion pair with the weakly hydrated ultrafast molecule-rotor-based organic cation, Thioflavin-T, which in turn leads to an aggregate assembly that provides a fluorescence turn-on response towards perrhenate. The sensing response of Thioflavin-T has been found to be quite selective towards the perrhenate anion when tested against anions that are ubiquitously present in the environment, such as chloride, nitrate, and sulfate anions. The formation of self-assembled Thioflavin-T aggregates has also been investigated by time-resolved emission and temperature-dependent measurements.