Crystal structure of a phenoxyl radical complex relevant to the metal site of the galactose oxidase enzyme: A facile one-pot synthesis, evidence for hydrogen atom transfer and DNA cleavage via self-activation.

Copper complexes [Cu(L1H)ClO4] (1) and [Cu(L2)NO3] (2), which are relevant to the metal site of the galactose oxidase enzyme, were synthesized and characterized by different spectroscopic methods. L1H2 and L2H2 [where L1H2 stands for 2,2'-((1E,1'E)(2,2'-(pyridine-2,6-diyl)bis(2-phenylhydrazin-2-yl-1-ylidene))bis(methanylylidene))diphenol and L2H2 stands for 6,6'-((1E,1'E)-(2,2'-(pyridine-2,6-diyl)bis(2-phenylhydrazin-2-yl-1-ylidene))bis(methanylylidene))bis(2,4-di-tert-butylphenol), H stands for dissociable proton] are pentadentate ligands. These ligands provide pyridyl N, two imine N, and two non-innocent phenoxyl and phenolato O donors, forming complex 1 as a non-radical complex, while complex 2 is a phenoxyl radical complex. The molecular structures of complexes 1 and 2 were authenticated by X-ray crystallography. Benzyl alcohol oxidation was investigated, and the conversion of 9,10-dihydroanthracene to anthracene was examined to scrutinize the H-atom abstraction reaction. Nuclease activity with complexes 1 and 2 was investigated by self-activated plasmid DNA (pBR322) cleavage. Non-innocent properties of the ligand-containing phenolato function were investigated by DFT calculations.

Effect of cycloastragenol and punicalagin on Prp(106-126) and Aß(25-35) oligomerization and fibrillizaton.

Numerous neurological disorders, including prion, Parkinson's, and Alzheimer's disease (AD), are identified as being caused by alterations in protein conformation, aggregation, and metal ion dyshomeostasis. Recent years have seen a significant increase in the exploration and study of natural products (NPs) from plant and microbial sources for their therapeutic potential against several diseases, including cancer, diabetes, cardiovascular disease, and neurodegenerative diseases. In this study, we have examined the effect of two NPs, cycloastragenol (CAG) and punicalagin (PCG), on the metal-induced oligomerization and aggregation of Aß25-35 and PrP106-126 peptides. The peptide aggregation and inhibitory properties of both NPs were examined by the thioflavin-T (ThT) assay, MALDI-TOF, circular dichroism (CD) spectroscopy, and transmission electron microscopy (TEM). Among the two NPs, PCG significantly binds to the peptides, chelates metal ions (Cu2+ and Zn2+), inhibits peptide aggregation, substantially reduces oxidative stress, and controls the production of reactive oxygen species (ROS). Both NPs exhibited low cytotoxicity and prominently mitigated peptide-mediated cell cytotoxicity in hippocampal neuronal HT-22 cells by covalent bonding and hydrophobic interactions.

Inhibition of amyloid ß1-42 peptide aggregation by newly designed cyclometallated palladium complexes.

Uncontrolled amyloid aggregation is a frequent cause of neurodegenerative disorders such as prions and Alzheimer's disease (AD). As a result, many drug development approaches focus on evaluating novel molecules that can alter self-recognition pathways. Herein, we designed and synthesized the cyclometallated pyrene (Pd-1 and Pd-3) and anthracene (Pd-2) based palladium complexes ([Pd((L1)Cl] Pd-1, [Pd(L2)Cl](Pd-2), and [Pd(L3)Cl] (Pd-3)). This study explores the effect of these complexes on the aggregation, fibrillation, and amyloid formation of bovine serum albumin (BSA) and Aß1-42 peptide. Several spectroscopic methods were used to characterize all the Pd-complexes, and the molecular structure of Pd-3 was determined by X-ray crystallography. The secondary structures were studied using circular dichroism (CD) and transmission electron microscopy (TEM), while amyloid aggregation and inhibitory activities were investigated using the Thioflavin-T (ThT) fluorescence assay. Molecular docking of the Pd-complex (Pd-3) was done using fibril (PDB: 2BEG) and monomeric (PDB: 1IYT) peptides using Auto-dock Vina. As a result, the hydrogen bonding and hydrophobic interaction between the aromatic rings of the Pd-complexes and the amino acids of amyloid-ß peptides significantly reduced the production of ordered ß-sheets of amyloid fibrils and protein aggregation in the presence of Pd-2 and Pd-3 complexes.

Effect of Implementation of an Eyecare Bundle on Incidence of Exposure Keratopathy in Intensive Care Unit of Tertiary Care Center in North India.

Background: Lack of eyecare protective measures especially in unconscious and sedated critically ill patients, make them prone to ocular surface diseases (OSDs), e.g., exposure keratopathy. This study is aimed to frame an algorithm-based approach to eyecare via eyecare bundle to bring down the burden of OSDs in critically ill patients especially in resource-limited settings. Materials and methods: After clearance from institutional ethical committee, a quasi-experimental single center study was conducted over a period of 6 months. Incidence of exposure keratopathy was calculated before and after induction of eyecare bundle and was compared. Statistical analysis was done using SPSS software v20. p-value of less than 0.05 was considered significant. Results: A total of 218 patients were enrolled in the study after obtaining informed written consent and after fulfilling inclusion criteria. Patients were divided into control and experimental groups, with baseline characteristics similar in both the groups, respectively, in terms of gender, age (40 years), APACHE II score, and specialty distribution except predominantly medical patients in experimental group. In control group (n = 99), total 69 patients (41 medical and 28 surgical) developed exposure keratopathy, while in experimental group (n = 109) only 15 patients (6 medical and 9 surgical) developed exposure keratopathy, hence a significant reduction was observed. Further follow-up of patients in the experimental group was also done on Days 5 and 7, respectively. Conclusion: The proposed protocolized algorithm-based eyecare bundle significantly reduced the incidence of exposure keratopathy in sedated, mechanically ventilated, and vulnerable critically ill patients. How to cite this article: Sama S, Abrol R, Dhasmana R, Sharma N, Khandhuri S, Chauhan R, et al. Effect of Implementation of an Eyecare Bundle on Incidence of Exposure Keratopathy in Intensive Care Unit of Tertiary Care Center in North India. Indian J Crit Care Med 2023;27(6):426-432.

Polypharmacy and cumulative anticholinergic burden in older adults hospitalized with fall.

Introduction: Polypharmacy is a growing phenomenon associated with adverse effects in older adults. We assessed the potential confounding effects of cumulative anticholinergic burden (ACB) in patients who were hospitalized with falls. Methods: A noninterventional, prospective cohort study of unselected, acute admissions aged ≥ 65 years. Data were derived from electronic patient health records. Results were analyzed to determine the frequency of polypharmacy and degree of ACB and their relationship to falls risk. Primary outcomes were polypharmacy, defined as prescription of 5 or more regular oral medications, and ACB score. Key Results: Four hundred eleven (411) consecutive subjects were included, mean age 83.8 ± 8.0 years: 40.6% men. There were 38.4% patients who were admitted with falls. Incidence of polypharmacy was 80.8%, (88.0% and 76.3% among those admitted with and without fall, respectively). Incidence of ACB score of 0, 1, 2, ≥ 3 was 38.7%, 20.9%, 14.6%, and 25.8%, respectively. On multivariate analysis, age [odds ratio (OR) = 1.030, 95% CI:1.000 ~ 1.050, P = 0.049], ACB score (OR = 1.150, 95% CI:1.020 ~ 1.290, P = 0.025), polypharmacy (OR = 2.140, 95% CI:1.190 ~ 3.870, P = 0.012), but not Charlson Comorbidity Index (OR = 0.920, 95% CI:0.810 ~ 1.040, P = 0.172) were significantly associated with higher falls rate. Of patients admitted with falls, 29.8% had drug-related orthostatic hypotension, 24.7% had drug-related bradycardia, 37.3% were prescribed centrally acting drugs, and 12.0% were taking inappropriate hypoglycemic agents. Conclusion: Polypharmacy results in cumulative ACB and both are significantly associated with falls risk in older adults. The presence of polypharmacy and each unit rise in ACB score have a stronger effect of increasing falls risk compared to age and comorbidities.

Effect on neonatal sepsis following immediate kangaroo mother care in a newborn intensive care unit: a post-hoc analysis of a multicentre, open-label, randomised controlled trial.

Background: To implement the immediate Kangaroo mother care (iKMC) intervention in the previous multicentre, open-label, randomised controlled trial, the mother or a surrogate caregiver and neonate needed to be together continuously, which led to the concept of the Mother-Newborn Care Unit (MNCU). Health-care providers and administrators were concerned of the potential increase in infections caused by the continuous presence of mothers or surrogates in the MNCU. We aimed to assess the incidence of neonatal sepsis in sub-groups and the bacterial profile among intervention and control neonates in the study population. Methods: This is a post-hoc analysis of the previous iKMC trial, which was conducted in five level 2 Newborn Intensive Care Units (NICUs) one each in Ghana, India, Malawi, Nigeria, and Tanzania, in neonates with birth weight 1 to <1.8 kg. The intervention was KMC initiated immediately after birth and continued until discharge and compared to conventional care with KMC initiated after meeting stability criteria. The primary outcomes of this report were the incidence of neonatal sepsis in sub-groups, sepsis-related mortality and bacterial profile of isolates during hospital stay. The original trial is registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12618001880235) and the Clinical Trials Registry-India (CTRI/2018/08/01536). Findings: Between November 30, 2017, and January 20, 2020, 1609 newborns in the intervention group and in the control group 1602 newborns were enrolled in iKMC study. 1575 newborns in the intervention group and 1561 in the control group were clinically evaluated for sepsis. Suspected sepsis was 14% lower in intervention group in sub-group of neonates with birth weight 1.0-<1.5 kg; RR 0.86 (CI 0.75, 0.99). Among neonates with birth weight 1.5-<1.8 kg, suspected sepsis was reduced by 24%; RR 0.76 (CI 0.62, 0.93). Suspected sepsis rates were lower in intervention group than in the control group across all sites. Sepsis related mortality was 37% less in intervention group than the control group; RR 0.63 (CI 0.47-0.85) which was statistically significant. The intervention group had fewer cases of Gram-negative isolates (n = 9) than Gram positive isolates (n = 16). The control group had more cases of Gram-negative isolates (n = 18) than Gram positive (n = 12). Interpretation: Immediate Kangaroo Mother care is an effective intervention to prevent neonatal sepsis and sepsis related mortality. Funding: The original trial was funded by the Bill and Melinda Gates Foundation through a grant to the World Health Organization (grant No. OPP1151718).

Synthesis and CNS Activity of Phenytoin Derivatives.

BACKGROUND: The derivatives of Phenytoin conjugated with various anilines were synthesized. The synthesized derivatives were evaluated for different physicochemical parameters along with log P values using different software programs to discover their ability to cross the blood brain barrier. The pharmacological activities such as antianxiety, skeletal muscle relaxant and anticonvulsant were evaluated by using different models. OBJECTIVE: The new Phenytoin derivatives were synthesized and evaluated for different properties to predict CNS activity. The drugs synthesized by chloroacetylation and then different aniline were added to it. The compounds were evaluated for their different CNS activity by using different methods. METHODS: The compounds were synthesized by firstly chloroacetylating the phenytoin and then different substituted anilines were added to it. The compounds were evaluated for antianxiety activity, muscle relaxant activity and anticonvulsant activity by using different models. RESULTS: The number of derivatives of Phenytoin was synthesized and various physicochemical parameters were optimized which revealed that the compound containing chloro groups such as C2 and C5 exhibited significant potential when compared with the standard drug Diazepam. CONCLUSION: It was portrayed that the synthesis, computational studies and evaluation of anticonvulsant, antianxiety and skeletal muscle relaxant activity of new Phenytoin derivatives were carried out. The compounds were productively synthesized and portrayed by molecular docking studies. The compounds also exhibit mild to moderate similarity with respect to standard drug. The synthesized drugs have the potential to be optimized further to engender new scaffolds to treat various CNS disorders.

A Curious Case of Paroxysmal Painful Thumb: Glomus Tumor Re-visited.

Glomus tumor is a rare and benign vascular hamartoma originating from the neuro-myo-arterial apparatus of the glomus body in the reticular dermis. Most commonly, it presents as a solitary subungual lesion which is often painful and triggered by changes in temperature and pressure on the affected digit. However, multiple glomus tumors both digitally and elsewhere on the body which may or may not be painful are also known to occur. Due to its cryptic location and varied presentation, there is an invariable delay in the diagnosis and management of this condition. We report a case of glomus tumor in a 28-year-old woman presenting with paroxysmal painful lesion over her right thumb for 5 years.

Tumor Lymphatic Interactions Induce CXCR2-CXCL5 Axis and Alter Cellular Metabolism and Lymphangiogenic Pathways to Promote Cholangiocarcinoma.

Cholangiocarcinoma (CCA), or cancer of bile duct epithelial cells, is a very aggressive malignancy characterized by early lymphangiogenesis in the tumor microenvironment (TME) and lymph node (LN) metastasis which correlate with adverse patient outcome. However, the specific roles of lymphatic endothelial cells (LECs) that promote LN metastasis remains unexplored. Here we aimed to identify the dynamic molecular crosstalk between LECs and CCA cells that activate tumor-promoting pathways and enhances lymphangiogenic mechanisms. Our studies show that inflamed LECs produced high levels of chemokine CXCL5 that signals through its receptor CXCR2 on CCA cells. The CXCR2-CXCL5 signaling axis in turn activates EMT (epithelial-mesenchymal transition) inducing MMP (matrix metalloproteinase) genes such as GLI, PTCHD, and MMP2 in CCA cells that promote CCA migration and invasion. Further, rate of mitochondrial respiration and glycolysis of CCA cells was significantly upregulated by inflamed LECs and CXCL5 activation, indicating metabolic reprogramming. CXCL5 also induced lactate production, glucose uptake, and mitoROS. CXCL5 also induced LEC tube formation and increased metabolic gene expression in LECs. In vivo studies using CCA orthotopic models confirmed several of these mechanisms. Our data points to a key finding that LECs upregulate critical tumor-promoting pathways in CCA via CXCR2-CXCL5 axis, which further augments CCA metastasis.

Atypical presentation of COVID-19 in hospitalised older adults.

BACKGROUND: It is increasingly recognised that older patients may not present with typical symptoms of COVID-19. AIMS: This study aims to evaluate the incidence, characteristics and clinical outcome of older adults with atypical presentations of COVID-19. METHODS: A retrospective analysis of adults ≥ 65 years with confirmed COVID-19 admitted to our institution between 1 March and 24 April 2020 was performed. Patients were categorised into typical or atypical groups based on primary presenting complaint in the community. RESULTS: One hundred twenty-two patients (mean age 81 ± 8 years; 62 male) were included. Seventy-three (60%) were categorised into the typical group and 49 (40%) into the atypical group. In the atypical group, common presenting complaints were fall in 18 (36%), reduced mobility or generalised weakness in 18 (36%) and delirium in 11 (22%). Further assessment by paramedics and on admission found 32 (65%) to have typical features of COVID-19, fever being the most common, and 22 (44%) were hypoxic. This subset had worse outcomes than those in the typical group with a mortality rate of 50% versus 38%, respectively, although this was not statistically significant (P = 0.27). No significant difference in mortality or length of hospital stay between the groups was demonstrated. CONCLUSION: Older patients with atypical presentation of COVID-19 in the community are equally susceptible to poor outcomes. Early detection may improve outcomes and limit community transmission. Primary care practitioners should be vigilant and consider prompt onward referral.

Enhanced biosynthesis of quercetin occurs as A photoprotective measure in Lycopersicon esculentum mill. under Acute UV-B exposure

Lycopersicon esculentum respond to UV-B by enhanced synthesis of flavonoid quercetin, a strong antioxidant that helps the plants to well acclimatize to UV-B stress. Three weeks old plants of L. esculentum were subjected to acute UV-B irradiation for 20, 40 and 60 minutes daily until 28 days and analyzed for the morphological and biochemical changes. UV-B exposure for 40 and 60 minutes considerably affected the growth and biomass of L. esculentum. The leaves were deformed, developed chlorosis and abscised early as compared to the unexposed plants. Biomass declined by 35% and total chlorophyll decreased by 24.7% due to disintegration of chloroplasts. Enhancement was seen in the content of carotenoids, anthocyanins and total flavonoids by 15, 33.3 and 22.8%, respectively, which was attributed to the photoprotective role of these compounds as potential quenchers of excess excitation energy. Quercetin content decreased on UV-B exposure to 20 and 40 min, and thereafter increased significantly by 5.19% on 60 min of exposure. This pattern probably indicated that the over-expression of genes involved in its biosynthesis such as phenylalanine ammonia lyase (PAL), chalcone synthase (CHS), flavanone 3-hydroxylase (F3H) and dihydroflavonol 4-reductase (DFR) occurred only after certain threshold exposure (60 min), which could be the strategy for developing tolerance against UV-B stress in L. esculentum.

Prevalence and pattern of congenital heart disease in school children of eastern Uttar Pradesh.

BACKGROUND AND AIM: The prevalence of congenital heart disease (CHD) is not known in our country. The aim of present study was to find out the prevalence of CHD in school children of eastern Uttar Pradesh. METHOD: A team consisting of a cardiologist, physicians and junior residents visited schools in the area. All the children were examined for presence of cardiac murmur or history of heart disease or any intervention. Those with murmurs or previous history of heart disease were called to the Medical College Hospital for evaluation by ECG, chest X-ray and echocardiography for confirmation of the lesion. RESULTS: Out of 118,212 children examined, 142 were found to have CHD. The prevalence was 1.3 per 1000 children and the commonest lesions were ventricular and atrial septal defects, aortic stenosis with or without regurgitation, and pulmonary stenosis. CONCLUSION: CHD prevalence is 1.3 per 1000 school children that is nearly two and a half times more than that of RHD. Knowing it is important for development of facilities for CHD care in our setup.

Prevalence of rheumatic heart disease in school-going children of Eastern Uttar Pradesh.

BACKGROUND: Rheumatic heart disease is a major health problem in our country. There is evidence from South India that its prevalence is declining. This study attempts to confirm whether this is so in North India as well. METHODS AND RESULTS: A total of 118,212 (68,357 males, 49,855 females) schoolchildren in the age group of 4-18 years were examined for the presence of heart disease. Evaluation, including echocardiography, confirmed that of a total of 389 suspected to have heart disease, 61 had rheumatic heart disease. Thus, the prevalence of rheumatic heart disease was found to be approximately 0.5 per 1000 children. CONCLUSION: In a fairly large school survey conducted by us, the prevalence of rheumatic heart disease turned out to be approximately 0.5 per 1000 children. This is the lowest figure reported from our country so far and confirms the decline of this disease in our country.