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Thrombosis, the formation of blood clots in arteries or veins, poses a significant health risk by disrupting the blood flow. It can potentially lead to major cardiovascular complications such as acute myocardial infarction or ischemic stroke (arterial thrombosis) and deep vein thrombosis or pulmonary embolism (venous thrombosis). Nevertheless, over the course of several decades, researchers have observed an association between different cardiovascular events and neurodegenerative diseases, which progressively harm and impair parts of the nervous system, particularly the brain. Furthermore, thrombotic complications have been identified in numerous clinical instances of neurodegenerative diseases, particularly Alzheimer's disease, Parkinson's disease, multiple sclerosis, and Huntington's disease. Substantial research indicates that endothelial dysfunction, vascular inflammation, coagulation abnormalities, and platelet hyperactivation are commonly observed in these conditions, collectively contributing to an increased risk of thrombosis. Thrombosis can, in turn, contribute to the onset, pathogenesis, and severity of these neurological disorders. Hence, this concise review comprehensively explores the correlation between cardiovascular diseases and neurodegenerative diseases, elucidating the cellular and molecular mechanisms of thrombosis in these neurodegenerative diseases. Additionally, a detailed discussion is provided on the commonly employed antithrombotic medications in the context of these neuronal diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Platelets are essential component of circulation that plays a major role in hemostasis and thrombosis. During activation and its demise, platelets release platelet-derived microvesicles, with lysophosphatidylcholine (LPC) being a prominent component in their lipid composition. LPC, an oxidized low-density lipoprotein, is involved in cellular metabolism, but its higher level is implicated in pathologies like atherosclerosis, diabetes, and inflammatory disorders. Despite this, its impact on platelet function remains relatively unexplored. To address this, we studied LPC's effects on washed human platelets. A multimode plate reader was employed to measure reactive oxygen species and intracellular calcium using H 2 DCF-DA and Fluo-4-AM, respectively. Flow cytometry was utilized to measure phosphatidylserine expression, mitochondrial membrane potential (ΔΨm), and mitochondrial permeability transition pore (mPTP) formation using FITC-Annexin V, JC-1, and CoCl 2 /calcein-AM, respectively. Additionally, platelet morphology and its ultrastructure were observed via phase contrast and electron microscopy. Sonoclot and light transmission aggregometry were employed to examine fibrin formation and platelet aggregation, respectively. The findings demonstrate that LPC induced oxidative stress and increased intracellular calcium in platelets, resulting in increased phosphatidylserine expression and reduced ΔΨm. LPC triggered caspase-independent platelet death and mPTP opening via cytosolic and mitochondrial calcium, along with microvesiculation and reduced platelet counts. LPC increased the platelet's size, adopting a balloon-shaped morphology, causing membrane fragmentation and releasing its cellular contents, while inducing a pro-coagulant phenotype with increased fibrin formation and reduced integrin αIIbβ3 activation. Conclusively, this study reveals LPC-induced oxidative stress and calcium-mediated platelet death, necrotic in nature with pro-coagulant properties, potentially impacting inflammation and repair mechanisms during vascular injury., (© 2024 International Federation for Cell Biology.)

In this article, we describe a novel case of SARS-CoV-2-associated-hemophagocytic lymphohistiocytosis (HLH) complicated by posterior reversible encephalopathy syndrome (PRES). Initially diagnosed with multisystem inflammatory response in children (MIS-C), the patient received a large corticosteroid dose days before the onset of neurological symptoms. After developing PRES, the patient was treated with antihypertensives, antiepileptics, dexamethasone, and anakinra, leading to neurologic normalization. We propose that given the challenging diagnostic picture of PRES developing in patients with HLH or MIS-C, institutionalized standards for blood pressure management during corticosteroid induction may significantly improve outcomes in patients being treated for hyperinflammatory syndromes who develop neurological symptoms., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Ross M. Perry et al.)

We report a novel mutation on α2-globin gene leading to an elongated α-chain. This novel frameshift mutation was detected in a 13-year-old boy from Balkh province, Afghanistan. DNA analysis identified an insertion of thymine (T) at codon 132 [ HBA2 :c.396dup (p.Val134fs)]. We named the novel hemoglobin variant 'Hemoglobin Balkh' after the geographic location from which the patient originated. This novel variant was found in association with α3.7 kb α-globin gene deletion, suggesting a compound heterozygous state that contributes to the patient's clinical presentation.

Parkinson's disease (PD) is a predominant neuromotor disorder characterized by the selective death of dopaminergic neurons in the midbrain. The majority of PD cases are sporadic or idiopathic, with environmental toxins and pollutants potentially contributing to its development or exacerbation. However, clinical PD patients are often associated with a reduced stroke frequency, where circulating blood platelets are indispensable. Although platelet structural impairment is evident in PD, the platelet functional alterations and their underlying molecular mechanisms are still obscure. Therefore, we investigated rotenone (ROT), an environmental neurotoxin that selectively destroys dopaminergic neurons mimicking PD, on human blood platelets to explore its impact on platelet functions, thus replicating PD conditions in vitro. Our study deciphered that ROT decreased thrombin-induced platelet functions, including adhesion, activation, secretion, and aggregation in human blood platelets. As ROT is primarily responsible for generating intracellular reactive oxygen species (ROS), and ROS is a key player regulating the platelet functional parameters, we went on to check the effect of ROT on platelet ROS production. In our investigation, it became evident that ROT treatment resulted in the stimulation of ROS production in human blood platelets. Additionally, we discovered that ROT induced ROS production by augmenting Ca 2+ mobilization from inositol 1,4,5-trisphosphate receptor. Apart from this, the treatment of ROT triggers protein kinase C associated NADPH oxidase-mediated ROS production in platelets. In summary, this research, for the first time, highlights ROT-induced abnormal platelet functions and may provide a mechanistic insight into the altered platelet activities observed in PD patients., (© 2024 Wiley Periodicals LLC.)

Neurodegenerative diseases (NDDs) are specific brain disorders characterized by the progressive deterioration of different motor activities as well as several cognitive functions. Current conventional therapeutic options for NDDs are limited in addressing underlying causes, delivering drugs to specific neuronal targets, and promoting tissue repair following brain injury. Due to the paucity of plausible theranostic options for NDDs, nanobiotechnology has emerged as a promising field, offering an interdisciplinary approach to create nanomaterials with high diagnostic and therapeutic efficacy for these diseases. Recently, two-dimensional nanomaterials (2D-NMs) have gained significant attention in biomedical and pharmaceutical applications due to their precise drug-loading capabilities, controlled release mechanisms, enhanced stability, improved biodegradability, and reduced cell toxicity. Although various studies have explored the diagnostic and therapeutic potential of different nanomaterials in NDDs, there is a lack of comprehensive review addressing the theranostic applications of 2D-NMs in these neuronal disorders. Therefore, this concise review aims to provide a state-of-the-art understanding of the need for these ultrathin 2D-NMs and their potential applications in biosensing and bioimaging, targeted drug delivery, tissue engineering, and regenerative medicine for NDDs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the past three decades, interest in using carbon-based nanomaterials (CBNs) in biomedical application has witnessed remarkable growth. Despite the rapid advancement, the translation of laboratory experimentation to clinical applications of nanomaterials is one of the major challenges. This might be attributed to poor understanding of bio-nano interface. Arguably, the most significant barrier is the complexity that arises by interplay of several factors like properties of nanomaterial (shape, size, surface chemistry), its interaction with suspending media (surface hydration and dehydration, surface reconstruction and release of free surface energy) and the interaction with biomolecules (conformational change in biomolecules, interaction with membrane and receptor). Tailoring a nanomaterial that minimally interacts with protein and lipids in the medium while effectively acts on target site in biological milieu has been very difficult. Computational methods and artificial intelligence techniques have displayed potential in effectively addressing this problem. Through predictive modelling and deep learning, computer-based methods have demonstrated the capability to create accurate models of interactions between nanoparticles and cell membranes, as well as the uptake of nanomaterials by cells. Computer-based simulations techniques enable these computational models to forecast how making particular alterations to a material's physical and chemical properties could enhance functional aspects, such as the retention of drugs, the process of cellular uptake and biocompatibility. We review the most recent progress regarding the bio-nano interface studies between the plasma proteins and CBNs with a special focus on computational simulations based on molecular dynamics and density functional theory., (Copyright © 2024. Published by Elsevier Inc.)

Platelets, derived from bone marrow megakaryocytes, are essential for vascular integrity and play multifaceted roles in both physiological and pathological processes within the vasculature. Despite their small size and absence of a nucleus, platelets are increasingly recognized for their diverse immune functions. Recent research highlights their pivotal role in interactions with various immune cells, including professional cells like macrophages, dendritic cells, natural killer cells, T cells, and B cells, influencing host immune responses. Platelets also engage with non-professional immune cells, contributing to immune responses and structural maintenance, particularly in conditions like inflammation and atherosclerosis. This review underscores the emerging significance of platelets as potent immune cells, elucidating their interactions with the immune system. We explore the mechanisms of platelet activation, leading to diverse functions, such as aggregation, immunity, activation of other immune cells, and pathogen clearance. Platelets have become the predominant immune cells in circulation, involved in chronic inflammation, responses to infections, and autoimmune disorders. Their immunological attributes, including bioactive granule molecules and immune receptors, contribute to their role in immune responses. Unlike professional antigen-presenting cells, platelets process and present antigens through an MHC-I-dependent pathway, initiating T-cell immune responses. This review illuminates the unique features of platelets and their central role in modulating host immune responses in health and disease., (Copyright © 2024. Published by Elsevier Inc.)

Platelet-derived microvesicles (PMVs) represent a significant proportion of microvesicles in circulation and have been linked to various pathophysiological complications. Recent research suggests that PMVs carry significant amounts of cargo that can affect cellular functions by influencing calcium oscillations in target cells. As calcium is involved in multiple cellular processes, including hemostasis and thrombosis, this study aimed to investigate the impact of PMVs on platelet calcium mobilization. The study found that PMVs increase platelet intracellular calcium levels via both intracellular storage and extracellular space in a dose-dependent manner. The study highlighted the critical role of the dense tubular system, acidic vacuoles, mitochondrial stores, and store-operated calcium entry (SOCE) in PMV-mediated calcium release in human platelets. Moreover, the study revealed that PMV-induced calcium rise in platelets does not occur via sarcoendoplasmic reticulum calcium ATPase, and extracellular calcium addition further increases the calcium level in platelets, demonstrating the involvement of SOCE. These findings provide insights into the platelet stimulation signaling mechanisms and contributes to our understanding of platelet and cell behavior when exposed to PMV-rich environments., (© 2023 International Federation of Cell Biology.)

The blood platelet plays an important role but often remains under-recognized in several vascular complications and associated diseases. Surprisingly, platelet hyperactivity and hyperaggregability have often been considered the critical risk factors for developing vascular dysfunctions in several neurodegenerative diseases (NDDs) like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, platelet structural and functional impairments promote prothrombotic and proinflammatory environment that can aggravate the progression of several NDDs. These findings provide the rationale for using antiplatelet agents not only to prevent morbidity but also to reduce mortality caused by NDDs. Therefore, we thoroughly review the evidence supporting the potential pleiotropic effects of several novel classes of synthetic antiplatelet drugs, that is, cyclooxygenase inhibitors, adenosine diphosphate receptor antagonists, protease-activated receptor blockers, and glycoprotein IIb/IIIa receptor inhibitors in NDDs. Apart from this, the review also emphasizes the recent developments of selected natural antiplatelet phytochemicals belonging to key classes of plant-based bioactive compounds, including polyphenols, alkaloids, terpenoids, and flavonoids as potential therapeutic candidates in NDDs. We believe that the broad analysis of contemporary strategies and specific approaches for plausible therapeutic treatment for NDDs presented in this review could be helpful for further successful research in this area., (© 2023 Wiley Periodicals LLC.)

Context: The potential of graphene derivatives for theranostic applications depends on their compatibility with cellular and biomolecular components. Lysophosphatidylcholine (LPC), a lipid component present in oxidized low-density lipoproteins, microvesicles and free circulation in blood, plays a critical role in the pathophysiology of various diseases. Using density functional theory-based methods, we systematically investigated the interaction of atherogenic LPC molecule with different derivatives of graphene, including pristine graphene, graphene with defect, N-doped graphene, amine-functionalized graphene, various graphene oxides and hydroxylated graphene oxides. We observed that the adsorption of LPC on graphene derivatives is highly selective based on the orientation of the functional groups of LPC interacting with the surface of the derivatives. Hydroxylated graphene oxide exhibited the strongest interaction with LPC with adsorption energy of - 2.1 eV due to the interaction between the hydroxyl group on graphene and the phosphate group of LPC. The presence of aqueous medium further enhanced this interaction indicating favourable adsorption of LPC and graphene oxide in biological systems. Such strong interaction leads to substantial change in the electronic structure of the LPC molecule, which results in the activation of this molecule. In contrast, amine-modified graphene showed the least interaction. These theoretical results are in line with our experimental fluorescence spectroscopic data of LPC/1-anilino-8-napthalene sulfonic acid complex. Our present comprehensive investigation employing both theoretical and experimental methods provides a deeper understanding of graphene-lipid interaction, which holds paramount importance in the design and fabrication of graphene-based nanomaterials for biomedical applications., Methods: In this study, we employed the density functional theory-based methods to investigate the electronic and structural properties of graphene derivatives and LPC molecule using the Quantum Espresso package. The exchange-correlation functional was described within generalized gradient approximation (GGA) as parameterized by Perdew, Burke and Ernzerhof (PBE). The valence electrons were represented using plane wave basis sets. `The Grimme's dispersion method was used to include the van der Waals dispersion correction., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Parkinson's disease (PD) is a progressive neuronal illness often linked to increased cardiovascular complications, such as myocardial infarction, cardiomyopathy, congestive heart failure, and coronary heart disease. Platelets, which are the essential components of circulating blood, are considered potential players in regulating these complications, as platelet dysfunction is evident in PD. These tiny blood cell fragments are supposed to play a crucial role in these complications, but the underlying molecular processes are still obscure., Methods: To gain a better understanding of platelet dysfunction in PD, we investigated the impact of 6-hydroxydopamine (6-OHDA), an analog of dopamine that simulates PD by destroying dopaminergic neurons, on human blood platelets. The levels of intraplatelet reactive oxygen species (ROS) were assessed using H 2 DCF-DA (20 μM), while mitochondrial ROS was evaluated using MitoSOX™ Red (5 μM), and intracellular Ca 2+ was measured with Fluo-4-AM (5 μM). The data were acquired through the use of both a multimode plate reader and a laser-scanning confocal microscope., Results: Our findings showed that 6-OHDA treatment increased the production of ROS in human blood platelets. The increase in ROS was confirmed by the ROS scavenger, NAC, and was also reduced by inhibiting the NOX enzyme with apocynin. Additionally, 6-OHDA potentiated mitochondrial ROS production in platelets. Furthermore, 6-OHDA triggered the intraplatelet Ca 2+ elevation. This effect was mitigated by the Ca 2+ chelator BAPTA, which decreased the ROS production triggered by 6-OHDA in human blood platelets, while the IP 3 receptor blocker, 2-APB, reduced the formation of ROS induced by 6-OHDA., Conclusion: Our findings suggest that the 6-OHDA-induced ROS production is regulated by the IP 3 receptor-Ca 2+ -NOX signaling axis in human blood platelets, where the platelet mitochondria also play a significant role. This observation provides a crucial mechanistic understanding of the altered platelet activities that are commonly observed in PD patients., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The quest for an effective regional anaesthesia technique in breast surgery has always been eluded by its apparent complexity. Various techniques had been described as anaesthetic techniques for breast cancer surgeries. Fascial plane blocks had been used as analgesic techniques for this procedure. We describe a case series of 12 patients who were given a combination of erector spinae plane block (ESP), Pectoralis I (Pecs I) and serratus anterior plane (SAP) block as sole anaesthetic technique with high risk surgical morbidity. Two patients had discomfort during retraction of axillary apex towards the end of surgery, and one patient had discomfort during medial parasternal incision, which needed a single bolus of low dose ketamine injection. Combined fascial plane blocks could be effectively utilized as a sole regional anesthesia modality for breast cancer surgeries with mild sedation., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Anaesthesiology Clinical Pharmacology.)

Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses of spike protein mutations in the significant variant clade of SARS-CoV-2, using the data available on the Nextstrain server. We selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These mutations were chosen based on their global entropic score, emergence, spread, transmission, and their location in the spike receptor binding domain (RBD). The relative abundance of these mutations was mapped with global mutation D614G as a reference. Our analyses suggest the rapid emergence of newer global mutations alongside D614G, as reported during the recent waves of COVID-19 in various parts of the world. These mutations could be instrumentally imperative for the transmission, infectivity, virulence, and host immune system's evasion of SARS-CoV-2. The probable impact of these mutations on vaccine effectiveness, antigenic diversity, antibody interactions, protein stability, RBD flexibility, and accessibility to human cell receptor ACE2 was studied in silico. Overall, the present study can help researchers to design the next generation of vaccines and biotherapeutics to combat COVID-19 infection.

Platelet-derived microvesicles (PMVs) are the most abundant microvesicles in circulation, originating from blood platelets via membrane blebbing. PMVs act as biological cargo carrying key molecules from platelets, including immunomodulatory molecules, growth factors, clotting molecules, and miRNAs that can regulate recipient cellular functions. Formation and release of PMVs play an essential role in the pathophysiology of vascular diseases such as hemostasis, inflammation, and thrombosis. Platelet activation is considered the critical event in thrombosis, and a growing number of evidence suggests that oxidative stress-mediated signaling plays a significant role in platelet activation. Ca 2+ is a notable player in the generation of ROS in platelets. Reports have established that microvesicles exhibit dual nature in redox mechanisms as they possess both pro-oxidant and antioxidant machinery. However, the impact of PMVs and their ROS machinery on platelets is still a limited explored area. Here, we have demonstrated that PMVs mediate platelet activation via intracellular ROS generation. PMVs interacted with platelets and induced calcium-mediated intracellular ROS production via NADPH oxidase (NOX), leading to platelet activation. Our findings will open up new insights into the tangible relationship of PMVs with platelets and will further contribute to the therapeutic aspects of PMVs in vascular injury and tissue remodeling., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is considered one of the most common causes of dementia worldwide, accounting for about 80 % of all dementia cases. AD is manifested by the extraneuronal deposition of senile plaques of amyloid beta (Aβ) and intraneuronal accumulation of neurofibrillary tangles of phosphorylated tau. The impaired proteostasis of these filamentous Aβ and tau is significantly regulated by reactive oxygen species (ROS). ROS-induced oxidative stress (OS) is the cardinal cause behind neuroinflammation-triggered neurodegeneration during AD. Besides ROS-induced neuro-inflammation, AD is also associated with cerebrovascular dysfunction, where platelet primarily plays a significant role in blood-vessel integrity and tissue repair. Though platelets are the circulatory cell fragments that play predominant roles in thrombosis and hemostasis, their contributions to other physiological functions are also being elucidated. Surprisingly, platelets contribute about 90 % of the circulatory Aβ and share striking similarities with neurons in several aspects, including different neurotransmitters and their cognate receptors, thus considering platelets as potential peripheral models for AD. Interestingly, platelet structural and functional dysfunctions are evident in AD, where ROS production is associated with platelet hyperactivity. Although activated platelet carries several vital enzymes and immunomodulatory molecules, which can potentially exacerbate OS-mediated neuronal damage, and neurodegeneration, their mechanism of action and mode of progression, are still obscure. Therefore, in this review, we have described the detailed role of OS and platelet in AD, addressing the therapeutic approach and molecular mechanism of platelet-mediated ROS generation as a contributing factor in aggravating the disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: Passage of double-lumen tubes (DLT) can be challenging in patients with limited glottis view. This study aims to determine the usefulness of McGrath® MAC videolaryngoscope (VL) in cases with limited glottis view on direct laryngoscopy with Macintosh blade., Material and Methods: After study approval and registration of trial, consent was sought from all adult patients planned for elective DLT insertion for lung isolation during the course of general anesthesia. Patients not consenting, less than 18 years, with anticipated difficult mask ventilation or need for rapid sequence induction were excluded. Following routine anesthetic induction, laryngoscopy was attempted by an experienced anesthesiologist using Macintosh scope. If the view obtained was Cormack and Lehane (CL) view IIB and above or the attempt at intubation using DLT failed despite a CL I/IIA view, the patient was included in the trial. The laryngoscope was removed and after ensuring adequate oxygenation and depth of anesthesia, intubation was attempted using McGrath® MAC VL. The percentage of glottis opening (POGO) score was noted for both the scopes., Results: DLT insertion was attempted in 76 patients in the study period. Eight patients were included in the trial on account of limited glottis view/failure with Macintosh scope. Insertion of DLT with McGrath MAC was tried only in six patients, in two patients, the VL was not available for use. The mean (standard deviation) POGO score with Macintosh scope was 9 (±20), which significantly improved with the use of VL to 71 (±24), P = 0.01., Conclusion: McGrath MAC is helpful in inserting DLT in patients with limited glottis view with Macintosh scope., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Anaesthesiology Clinical Pharmacology.)

Parkinson's disease (PD) is the second-most-common neurodegenerative disease characterized by motor and non-motor dysfunctions, which currently affects about 10 million people worldwide. Gradual death and progressive loss of dopaminergic neurons in the pars compacta region of substantia nigra result in striatal dopamine deficiency in PD. Specific mutation with further aggregation of α-synuclein in the intraneuronal inclusion bodies is considered the neuropathological hallmark of this disease. PD is often associated with various organelle dysfunctions inside a dopaminergic neuron, including mitochondrial damage, proteasomal impairment, and production of reactive oxygen species, thus causing subsequent neuronal death. Apart from several genetic and non-genetic risk factors, emerging research establishes an association between cardiovascular diseases, including coronary heart disease, myocardial infarction, congestive heart failure, and ischemic stroke with PD. The majority of these cardiovascular diseases have an origin from atherosclerosis, where endothelial dysfunction following thrombus formation is significantly regulated by blood platelet. This non-nucleated cell fragment expresses not only neuron-specific molecules and receptors but also several PD-specific biomarkers such as α-synuclein, parkin, PTEN-induced kinase-1, tyrosine hydroxylase, dopamine transporter, thus making platelet a suitable peripheral model for PD. Besides its similarity with a dopaminergic neuron, platelet structural alterations, as well as functional abnormalities, are also evident in PD. However, the molecular mechanism behind platelet dysfunction is still elusive and quite controversial. This state-of-the-art review describes the detailed mechanism of platelet impairment in PD, addressing the novel platelet-associated therapeutic drug candidates for plausible PD management., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Acute lymphocytic leukemia (ALL) is a common pediatric cancer diagnosis with excellent survival outcomes but significant morbidity, particularly during the induction phase of chemotherapy. Central venous sinus thrombosis (CVST) is a known potential complication of induction therapy; however, it occurs rarely and may be difficult to diagnose, particularly in young children who have limited verbal skills. Herein, we report a case of CVST in a child with B-cell ALL undergoing induction chemotherapy whose main symptoms were headache and a change in the appearance of his artwork noticed by his parents. This astute observation by the child's parents played a critical role in his diagnosis, allowing prompt treatment and eventual recovery., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report for this paper. This paper did not receive any sources of funding. The information herein was not submitted for publication or presentation to any other journal or meeting., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Cancer refers to the division of abnormal cells at an uncontrollable rate that possesses the ability to infiltrate and destroy normal tissues. It frequently spreads to normal tissues throughout the body, a condition known as metastasis, which is a significant concern. It is the second leading cause of mortality globally and treatment therapy can assist in improving survival rates. Exosomes are the extracellular vesicles secreted by several cells that act as messengers between cells. When engineered, exosomes act as promising drug delivery vehicles that help achieve targeted action at the tumour site and reduce the limitations of conventional treatments such as castration, chemotherapy, radiation, etc. The present review provides an overview of exosomes, the biogenesis, sources, isolation methods and characterization. The current status and applications of chemotherapeutic agents loaded, engineered exosomes in cancer treatment were convoluted., (Copyright © 2022. Published by Elsevier Inc.)

Development of economical and high-performance electrocatalysts for the oxygen evolution reaction (OER) is of tremendous interest for future applications as sustainable energy materials. Here, a unique member of efficient OER electrocatalysts has been developed based upon structurally versatile dumbbell-shaped ternary transition-metal (Cu, Ni, Co) phosphates with a three-dimensional (3D) (Cu 2 (OH)(PO 4 )/Ni 3 (PO 4 ) 2 ·8H 2 O/Co 3 (PO 4 ) 2 ·8H 2 O) (CNCP) structure. This structure is prepared using a simple aqueous stepwise addition of metal ion source approach. Various structural investigations demonstrate highly crystalline nature of the composite structure. Apart from the unique structural aspect, it is important that the CNCP composite structure has proved to be an excellent electrocatalyst for OER performance in comparison with its binary or constituent phosphate under alkaline and neutral conditions. Notably, the CNCP electrocatalyst displays a much lower overpotential of 224 mV at a current density of 10 mA cm -2 and a lower Tafel slope of 53 mV dec -1 with high stability in alkaline medium. In addition, X-ray photoelectron spectroscopy analysis suggested that the activity and long-term durability for the OER of the ternary 3D metal phosphate are due to the presence of electrochemically dynamic constituents such as Ni and Co and their resulting synergistic effects, which was further supported by theoretical studies. Theoretical calculations also reveal that the incredible OER execution was ascribed to the electron redistribution set off in the presence of Ni and Cu and the most favorable interaction between the *OOH intermediate and the active sites of CNCP. This work may attract the attention of researchers to construct efficient 3D ternary metal phosphate catalysts for various applications in the field of electrochemistry.

Introduction: Clot retraction is a pivotal process for haemostasis, where platelets develop a contractile force in fibrin meshwork and lead to the increased rigidity of clot. The pathophysiological alteration in contractile forces generated by the platelet-fibrin meshwork can lead to haemostatic disorders. Regardless of its utter significance, clot retraction remains a limited understood process owing to lack of quantification methodology. Sonoclot analysis is a point-of-care technique used in clinical laboratories for whole blood analysis that provides in vitro qualitative as well as quantitative assessment of coagulation process from initial fibrin formation to clot retraction., Methods: Human washed platelets were isolated by differential centrifugation method and analysed via optical imaging, microscopy and Sonoclot analysis using 1-2 × 10 8 /mL of washed platelets, 1 U/mL of thrombin, 1 mg/mL of fibrinogen and 1 mM of calcium chloride., Results: In this study, we demonstrate the novelty of this instrument in the quantitative evaluation of clot retraction in washed platelets and attempted to optimize the reference range of Sonoclot parameters including ACT - 87.3 ± 20.997, CR - 16.23 ± 3.538 and PF - 3.57 ± 0.629, (n = 10)., Discussion: Sonoclot analysis provides a simple and quantitative method to better understand in vitro clot retraction and its modulation by retraction components including platelet count, fibrinogen and platelet-fibrin interaction compared with existing conventional methods. Sonoclot may prove to be a valuable tool in thrombus biology research to understand fundamental basis of blood clot retraction., (© 2021 John Wiley & Sons Ltd.)

Wound healing is a complex physiological process in which the damaged or injured tissue is replaced or regenerated by new cells or existing cells respectively in their synthesized and secreted matrices. Several cells modulate the process of wound healing including macrophages, fibroblasts, and keratinocytes. Apart from these cells, platelet has been considered as a major cellular fragment to be involved in wound healing at several stages by secreting its granular contents including growth factors, thus resulting in coagulation, inflammation, and angiogenesis. A distant cell, which is gaining significant attention nowadays due to its resemblance with platelet in several aspects, is the neuron. Not only neurons but also glia cells are also confirmed to regulate wound healing at different stages in an orchestrated manner. Furthermore, these neurons and glia cells mediate wound healing inducing tissue repair and regeneration apart from hemostasis, angiogenesis, and inflammation by secreting various growth factors, coagulation molecules, immunomodulatory molecules as well as neurohormones, neuropeptides, and neurotrophins. Therefore, in wound healing platelets, neurons and glia cells not only contribute to tissue repair but are also responsible for establishing the wound microenvironment, thus affecting the proliferation of immune cells, fibroblast, and keratinocytes. Here in this review, we will enlighten the physiological roles of neurons and glia cells in coordination with platelets to understand various cellular and molecular mechanism in brain injury and associated neurocognitive impairments., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: In a day care setting, communication of preprocedure instructions prior to general anesthesia (GA) is critical. Verbal information may be inadequate at times leading to unnecessary rescheduling. The aim of the study is to evaluate the use of patient information leaflet (PIL) and its impact on rescheduling and patients' satisfaction levels., Material and Methods: Adult ASA I-III patients scheduled for elective day care Head Neck procedures such as direct laryngoscopy, examination under anesthesia, and biopsy under GA were recruited. In the outpatient department (OPD), the attending surgeons verbally instructed the patients as well as handed them the PIL. The process was streamlined over a month and thereafter patients' satisfaction levels and rescheduling rates were captured over 2 months. This was compared to the data from the pre-PIL phase., Result: Prior to PIL, 12% cases were rescheduled due to avoidable causes. After introducing of the PIL, only 8% case were rescheduled ( P = 0.02). There was a significant improvement seen in patient satisfaction with 89% patients reporting that the PIL was good or better while 77% were willing to recommend it to the others., Conclusion: PIL is an effective way of imparting perioperative instructions to patients which will improve not only satisfaction but also reduce patient rescheduling. The institution is in the process of implementing PIL to provide instructions to patient posted for day care procedures., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Anaesthesiology Clinical Pharmacology.)

After gaining entry through ACE2 aided by TMPRSS2, the SARS-CoV-2 causes serious complications of the cardiovascular system leading to myocarditis and other myocardial injuries apart from causing lung, kidney and brain dysfunctions. Here in this review, we are going to divulge the cellular and immunological mechanisms behind the cardiovascular, thrombotic and platelet impairments that are caused in COVID-19. In addition, we also propose the significance of various anti-platelet and anti-thrombotic phytochemicals in the treatment of COVID-19. The virus induces many immune-modulatory cytokines and chemokines which help in the intravascular coagulation and create a pro-thrombotic environment along with pulmonary embolism and thrombocytopenia. Different types of innate and adaptive immune cells and their granular contents regulate the pathophysiology of SARS-CoV-2 induced endothelial and platelet dysfunctions which correlate the involvement of platelets with myocardial injury and intravascular thrombi directly or indirectly. Hence, by exploiting the natural bioactive compounds from medicinal plants and inhibiting the platelet mediated thrombus formation can be beneficial for the treatment of SARS-CoV-2 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Beura, Panigrahi, Yadav and Singh.)

Background and Aims: It is essential that patients posted for day-care surgeries are adequately prepared preoperatively. Verbal information alone may not be always effective. This study aimed to prepare, validate, and evaluate the efficacy of a patient information leaflet (PIL) for patients undergoing day-care surgeries under general anesthesia (GA)., Material and Methods: After approval from the hospital ethics committee a PIL was prepared in English. Readability and design of the leaflet were checked using standard tests: Flesch readability ease test (FRE), Flesch Kincaid grade level (FKGL), and Baker Able leaflet design (BALD). It was translated into three regional languages. The PIL was tested among patients using a questionnaire. Seventy-nine adult patients posted for elective day-care procedures were included while emergency surgeries were excluded. Patient knowledge pre and post-PIL was compared using paired ' t ' test. The influence of age, gender, and education level on the usefulness of PIL were analyzed using the Chi-square test and knowledge was compared using ANOVA., Results: The English leaflet had an FRE Score of 63.9 and FKGL of 6.4, which is "standard". The BALD score for all leaflets was 25 ("above standard"). The overall knowledge scores significantly improved from 52.6% (preintervention) to 70.7% (postintervention), P < 0.001. Knowledge improvement was seen with the use of PIL in all four languages. Sixty eight percent of patients strongly recommended the PIL while 31% were willing to recommend it to others., Conclusion: The PILs developed in this study have standard readability, good design and validated for efficacy., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Anaesthesiology Clinical Pharmacology.)

Background: Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, short stature, congenital anomalies, and cancer predisposition. Most cases are due to mutations in genes encoding ribosomal proteins (RP) leading to RP haploinsufficiency. Effective treatments for the anemia of DBA include chronic red cell transfusions, long-term corticosteroid therapy, or hematopoietic stem cell transplantation. In a small patient series and in animal models, there have been hematologic responses to L-leucine with amelioration of anemia. The study objectives of this clinical trial were to determine feasibility, safety, and efficacy of L-leucine in transfusion-dependent patients with DBA., Procedure: Patients ≥2 years of age received L-leucine 700 mg/m 2 orally three times daily for nine months to determine a hematologic response and any improvement in growth (NCT01362595)., Results: This multicenter, phase I/II study enrolled 55 subjects; 43 were evaluable. There were 21 males; the median age at enrollment was 10.4 years (range, 2.5-46.1 years). No significant adverse events were attributable to L-leucine. Two subjects had a complete erythroid response and five had a partial response. Nine of 25, and 11 of 25, subjects experienced a positive weight and height percentile change, respectively, at the end of therapy., Conclusions: L-leucine is safe, resulted in an erythroid response in 16% of subjects with DBA, and led to an increase in weight and linear growth velocity in 36% and 44% of evaluable subjects, respectively. Further studies will be critical to understand the role of L-leucine in the management of patients with DBA., (© 2020 Wiley Periodicals LLC.)

Background: Emergency laparotomies present a challenge in pain management given sick patients, odd timings and poor outcomes. Current recommendations favour multimodal opioid-sparing analgesia following elective laparotomies. No recommendation exists for emergency surgeries., Methodology: After approval and registration of the trial, adult patients posted for emergency laparotomy in the hospital (tertiary centre for cancer care) starting August 2015, for 6 months, were included in this prospective study. Patients' details including indication for emergency surgery, preoperative haemodynamic parameters, baseline coagulation status were captured. Patients were followed for pain scores, satisfaction with pain management and outcome. The number of anaesthesiologists present and their experience concerning regional techniques were noted., Results: Intestinal obstruction was the commonest cause of emergency laparotomy. Most patients belonged to the ASA IE/IIE class (91%). Intraoperatively, opioids were the mainstay of pain management with an epidural catheter inserted in only 9% of cases even though most cases were conducted by anaesthesiologists confident/expert in thoracic epidural insertion. There was no correlation of choice of pain management technique with the time of surgery ( P = 0.22), ASA grading ( P = 0.28), predicted mortality by p-Possum scores ( P = 0.24). Pain at movement was moderate-severe in more than 50% of patients within the first 24 h. The regional group had better satisfaction when compared to opioid and non-opioid based management. ( P < 0.001)., Conclusion: Regional techniques for pain management in emergency laparotomies are less preferred, therefore, opioids are the mainstay. Lack of experience is essentially not the primary reason for regional techniques not gaining popularity. Pain management in this group needs a thorough re-evaluation., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Anaesthesia.)