Stimuli-responsive biotin-anchored prodrug for the targeted delivery of anti-cancer agent NBDHEX with turn-on NIR fluorescence.

Biothiol-activatable prodrug RK-296 was designed for the delivery of potent anti-cancer agent NBDHEX with concomitant turn-on near infrared (NIR) fluorescence. NBDHEX exhibits anti-cancer activity by selectively inhibiting glutathione-S-transferase pi (GSTP1), which is overexpressed in cancer cells and responsible for the inactivation of chemotherapeutic drugs. The sustained release of NBDHEX from the prodrug would be useful for ameliorating the off-target side-effects of NBDHEX.

Stress Levels in Mothers of Admitted Newborns in NICU and Effect of Counseling.

OBJECTIVES: To examine the effect of counseling on stress levels in mothers of neonates admitted to the Neonatal Intensive Care Unit (NICU). METHODS: This prospective research was carried out from January 2020 to December 2020 in a central India teaching hospital providing tertiary care. Parental Stressor Scale (PSS):NICU questionnaire was used to measure maternal stress among mothers of 540 admitted infants between 3 and 7 d of admission. Counseling was done at the time of recruitment and its effect was measured after 72 h and re-counseling was done. This cycle of stress assessment and counseling was repeated every 72 h till the baby was admitted in the NICU. Overall stress levels for each subscale were determined, and pre- and post-counseling stress was compared. RESULTS: For the subscales of sight and sound, appearance and behavior, change in the parental role, and staff behavior and communication, the median scores were 1.5 (IQR-1.2-1.88), 2.5 (2.3-2.9), 3.3 (3.0-3.6) and 1.3 (1.1-1.62), respectively indicating high stress in the parental role alteration. Counseling was effective in reducing stress levels among all mothers irrespective of various maternal factors (p <0.01). Stress reduces more with increasing number of counseling, as suggested by higher change in the stress score with increased number of counseling. CONCLUSIONS: This study shows that NICU mothers are under remarkable stress and repeated counseling sessions targeted at particular concerns might assist.

A Clinical Pharmacist-led Approach on Reducing Drug Related Problems Among Patients with Neurological Disorders: An Interventional Study.

Background: Neurological disorders are common in the general population and the majority of patients have other chronic diseases, necessitating the use of multiple medications, which increases the incidence of drug-related problems (DRPs). Studies from different countries discovered an average of 0.29-1.45 DRPs per patient admitted into the neurology unit. Objectives: To identify common DRPs and to evaluate the impact of clinical pharmacist's interventions in resolving the identified DRPs in patients with neurological disorders. Methods: A prospective interventional study was conducted in the Department of Neurology in a tertiary care teaching hospital in Southern India, for a period of six months. Patients aged ≥18 years and had been hospitalized for >24 h, were intensively monitored until discharge for the occurrence of any DRPs and pharmacist interventions were provided. The identified DRPs were classified according to Hepler and Strand's Classification. Results: A total of 310 prescriptions were reviewed, of which 174 patients (mean age 45.93 ± 2.49 years) experienced at least one DRP during their hospital stay. The average DRP per patient was found to be 1.75, with drug-drug interactions [254 (83%)] being the predominant DRPs, followed by adverse drug reactions [13 (4%)], and drug duplications [9 (3%)]. Most of the drug-drug interactions were pharmacokinetic [144 (56.69%)]. Hyponatremia [2 (15%)]; and nausea and vomiting [2 (15%)] were most commonly reported ADRs. All 306 DRPs involved active clinical pharmacist intervention, of which [275 (89.87%)] of pharmacists' interventions were accepted, which led to modification of the therapy. Conclusion: Monitoring the use of drugs allowed the clinical pharmacist to detect DRPs and to suggest interventions that promote rational drug prescribing, therapy optimization and enhanced patient safety.

Small-molecule organoselenocyanates: Recent developments toward synthesis, anticancer, and antioxidant activities.

Cellular redox homeostasis is very important for the overall cellular development, function, and oxidative stress often disrupts the process. Small-molecule organoselenium compounds exert key roles in maintaining the redox homeostasis during oxidative stress and cancer owing to their notable antioxidant activities. Among different organoselenium compounds, small-molecule organoselenocyanates have attracted much research attention due to their synthetic utilities and therapeutic potentials. Therefore, the development of convenient synthetic methodologies to different classes of organoselenocyanates from various precursors was explored over the years as useful synthetic building blocks. Additionally, considering their inherent redox and antioxidant properties, the development of biologically relevant organoselenocyanates upon their conjugation with the existing drugs and natural products has been chosen for enhancing the drug potencies and in ameliorating the drug-induced side-effects. In the present report, we have discussed some of the very recent and relevant developments on these aspects in a very concise manner.

Materiovigilance in Intensive Care Units: An Active Surveillance.

Background: Medical devices are the vital part of healthcare system. The use of medical devices is higher in the intensive care units leading to increased exposure rendering the exponential rise in incidence of medical device associated adverse events (MDAEs). Timely detection and reporting of MDAEs can help reduce the disease and associated liabilities. Objective: To determine the rate, patterns, and predictors of MDAEs. Methods: An active surveillance was carried out in the intensive care units (ICUs) of a tertiary care teaching hospital located in southern India. The patients were monitored for MDAEs which were reported based on MvPI guidance document 1.2. The predictors were calculated using an odds ratio at 95% confidence interval. Results: A total of 185 MDAEs were reported amongst 116 patients, of which the majority [74 (63.7%)] were males. Most of the MDAEs were attributed to urethral-catheters [42 (22.7%)] among which a high majority of 34 were associated with urinary tract infections (UTI), followed by ventilators [35 (18.9%)] with all events causing pneumonia. Urethral catheters and ventilators are both classified as categories B and C respectively based on device risk classification provided by the Indian Pharmacopoeia Commission (IPC). Over 58% of MDAEs were reported among the elderly. The causality assessment was possible for 90 (48.6%) MDAEs whereas 86 (46.4%) were probable. The majority of the MDAEs reported were serious [165 (89.2%)] and only [20 (10.8%)] were found to be non-serious on the severity scale. Most [104 (56.2%)] of the devices attributed to MDAEs were single-use devices, of which [103 (55.6%)] were destroyed and only [81 (43.7%)] were retained in healthcare facilities. Conclusions: Despite the best possible care in the intensive care units (ICUs), MDAEs are inevitable, adding to the burden of patients in terms of suffering, disease, extended hospital stay, and increased costs. MDAEs require rigorous monitoring of patients, especially in the elderly population and patients with increased exposure to multiple devices.

Albuminuria, glycemic variability and effect of flash glucose monitoring based decision making on short term glycemic variability in Indian type 2 diabetes patients: Indi-GlyVar study.

Aim and scope: Glycemic variability (GV) denotes the fluctuations in the glucose values around the baseline. High glycemic variability is associated with a higher risk of diabetes-associated complications. In this study, we sought to determine the impact of therapeutic interventions based on flash glucose monitoring on rapid, short-term glycemic variability. We also studied the prevalent albuminuria in diabetic kidney disease and its effect on glycemic variability. Methods: In a 14-day, single-center, prospective intervention study, we measured the GV indices at baseline (days 1-4) and ten days after ambulatory glucose profile-based intervention using flash glucose monitoring (Abbott Libre Pro, Abbott Diabetes Care, Alameda, California, USA) in patients with type 2 diabetes. An EasyGV calculator was used to estimate the flash glucose monitoring (FGM)-derived measures of GV. The primary outcome was to assess the impact of FGMS-based therapeutic interventions on glycemic variability markers: SD, mean amplitude of glycemic excursion [MAGE], continuous overall net glycemic action [CONGA], absolute means of daily differences [MODD], M value, and coefficient of variance [%CV], AUC below 70 mg/dl, low blood glucose index, AUC above 180 mg/dl [AUC >180], high blood glucose index [HBGI], and J index. Time-related matrices (time in range (%), time above range (%), and time below range (%) were also calculated from the ambulatory glucose profile. Renal function parameters (serum creatinine, estimated glomerular filtration rate, urine albumin excretion) were calculated. The GV with regard to albumin excretion rate was compared. Results: Fifty-eight T2DM patients (63.8%, males) with a mean age of 51.5 ± 11.9 years were studied. When compared with baseline (days 1-4), on day 14, there was a significant improvement in mean sensor glucose (mg/dl) median (IQR) [155 (116-247) vs 131 (103-163) (p ≤0.001)], JINDEX [15,878 (7,706-28,298) vs 8,812 (5,545-14,130) (p ≤0.001)], HBGI [361 (304-492) vs 334 (280-379) (p ≤0.001)], MAGE (mg/dl) [112 (8-146) vs 82 (59-109) (p ≤0.001)], M-value [2,477 (1,883-3,848) vs 2,156 (1,667-2,656) (p ≤ 0.001)], MAG (mg/dl) [111 (88-132) vs 88 (69-102) (p ≤ 0.001)]. Patients with albuminuria at baseline had high mean sensor glucose (mg/dl) median (IQR) [190 (131-200) vs 131 (112-156) (p = 0.001)], CONGA (mg/dl) median (IQR) [155 (101-165) vs 108 (83-120) (p = 0.001)], JINDEX, HBGI, MAGE (mg/dl), and M-value are, median (IQR) [20,715 (10,970-26,217 vs 91,118 (6,504-15,445)) (p ≤ 0.01)], [415 (338-423) vs 328 (292-354) (p = 0.001)], [125 (102-196) vs 103 (74-143) (p ≤ 0.01)], [3,014 (2,233-3,080) vs 2,132 (1,788-2,402) (p ≤0.01)], respectively. Conclusion: In type 2 diabetes, flash glucose monitoring-guided therapeutic interventions can reduce glycemic variability in a brief span (10 days) of time. Also, albuminuria in type 2 diabetes is associated with high glycemic variability. Reduced diabetes complications may ultimately result from this reduced glycemic variability.

The catalytic influence of phosphotungstic acid-functionalized Fe3O4 MNPs blended with TiO2 on the synthesis of novel spiro-acridines and the evaluation of their medicinal potential through molecular docking studies.

This manuscript describes an effective and rapid three-component synthesis of a novel series of spiro-acridine derivatives by integrating the pharmacologically dynamic hydantoin-phenytoin as the prime synthetic equivalent. The process was accelerated by Fe3O4@TiO2-PTA magnetic nanoparticles (MNPs), which acted as the heterogeneous catalytic system, under ultrasonic conditions. The reaction was performed in the green PEG-200 solvent under aerophilic conditions to obtain products with excellent yields. The characteristics of the synthesized magnetic nano-catalysts were corroborated through powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDAX), FT-IR, and VSM techniques. In addition, the structures of the synthesized compounds were ascertained on the basis of elemental analyses and spectro-analytical data (1H NMR, 13C NMR, and mass spectrometry). High yields, smaller E-factor, considerable atom economy, easy recovery, and recyclability of the catalyst and solvent are the captivating features of the developed protocol. Moreover, in view of the ongoing global research on COVID-19, herein, we tried to identify the potential sites of the synthesized moiety that can suitably fit the receptor sites of the main protease of SARS-CoV-2 (SARS-CoV-2 Mpro).