Demystifying the potential of lipid-based nanocarriers in targeting brain malignancies.

Drug targeting for brain malignancies is restricted due to the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which act as barriers between the blood and brain parenchyma. Certainly, the limited therapeutic options for brain malignancies have made notable progress with enhanced biological understanding and innovative approaches, such as targeted therapies and immunotherapies. These advancements significantly contribute to improving patient prognoses and represent a promising shift in the landscape of brain malignancy treatments. A more comprehensive understanding of the histology and pathogenesis of brain malignancies is urgently needed. Continued research focused on unraveling the intricacies of brain malignancy biology holds the key to developing innovative and tailored therapies that can improve patient outcomes. Lipid nanocarriers are highly effective drug delivery systems that significantly improve their solubility, bioavailability, and stability while also minimizing unwanted side effects. Surface-modified lipid nanocarriers (liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, lipid nanocapsules, lipid-polymer hybrid nanocarriers, lipoproteins, and lipoplexes) are employed to improve BBB penetration and uptake through various mechanisms. This systematic review illuminates and covers various topics related to brain malignancies. It explores the different methods of drug delivery used in treating brain malignancies and delves into the benefits, limitations, and types of brain-targeted lipid-based nanocarriers. Additionally, this review discusses ongoing clinical trials and patents related to brain malignancy therapies and provides a glance into future perspectives for treating this condition.

A case report of primary hydatidosis of ulna and adjacent soft tissue.

Hydatidosis, is a zoonotic disease prevalent in sheep-raising regions globally. Musculoskeletal hydatidosis is uncommon and usually remains asymptomatic over a long period. The detection of musculoskeletal hydatidosis often signifies extensive cyst spread within the bone marrow cavity, making treatment difficult with a high recurrence rate. Unlike the conventional surgical approach for visceral hydatid cysts, treating osseous hydatidosis requires a strategy akin to oncologic therapy. We report a rare case of primary hydatidosis affecting the ulna and adjacent soft tissue in a 58-year-old woman. She presented with a painless forearm mass evolving over six years, accompanied by recent onset tenderness and restricted elbow joint mobility. Imaging revealed a cystic mass in the forearm, an intra-ulnar bone lesion, and an olecranon fracture. The primary diagnosis of musculoskeletal hydatidosis was made based on clinical findings and radiological imaging. Treatment involved resection of 2/3 of the proximal ulna and pericystectomy for the soft tissue hydatid cyst. Diagnosis of musculoskeletal hydatidosis is vital for effective preoperative planning, as internal fixation often fails without eradicating the infestation. Treatment typically involves radical operation with wide excision of the affected bone and adjacent joint structures, coupled with chemotherapy. Clinicians in endemic regions should consider musculoskeletal hydatidosis in the differential diagnosis of osteolytic lesions and slow-growing cystic masses. Diagnosis relies on clinical, serological, and radiological assessments.

A Rare Case of Left Main Coronary Artery Coronary Sinus Fistula in an 85-Year-Old Female.

Coronary arteriovenous fistulas (CAVFs) are congenital or acquired communications between the coronary arteries and coronary venous system, and they can also include other cardiac structures or vasculature. We discuss a case of a large fistula between the left main coronary artery and the right atrium in a geriatric patient with a history of gastrointestinal arteriovenous malformations (AVM). The occurrence of CAVFs, an uncommon cardiac irregularity, is particularly infrequent among older adults. Typically, it is discovered by chance when investigating symptoms such as shortness of breath or chest pain, where coronary angiography is necessary to determine the most effective treatment strategy. This case highlights the possible utility of evaluating CAVFs in patients with a history of gastrointestinal AVM who similarly present with clinical symptoms of high-output heart failure. Once identified, this could simplify the treatment approach and improve communication between healthcare providers to minimize the risk of harm to the patient.

siRNA Treatments for Diabetic Neuropathy: Obstacles and Delivery Techniques.

Targeting genes using siRNA shows promise as an approach to alleviate symptoms of diabetic neuropathy. It focuses on neuropathies and distal symmetric polyneuropathy (DSPN) to explore the potential use of small interfering RNA (siRNA) as a treatment for diabetic neuropathy. Timely identification and management of neuropathy play a critical role in mitigating potential complications. RNAi success depends on understanding factors affecting small interfering RNA (siRNA) functionality and specificity. These include sequence space restrictions, structural and sequence features, mechanisms for nonspecific gene modulation, and chemical modifications. Addressing these factors enhances siRNA performance for efficient gene silencing and confidence in RNAi-mediated genomic studies. Diabetic retinopathy, particularly in South Asian, African, Latin American, and indigenous populations, is a significant concern due to its association with diabetes. Ethnicity plays a crucial role in its development and progression. Despite declining rates in the US, global trends remain concerning, and further research is needed to understand regional differences and reinforce ethnicity-based screening and treatment protocols. In this regard, siRNA emerges as a valuable instrument for early intervention strategies. While presenting promising therapeutic applications, siRNA utilization encounters challenges within insect pest control contexts, thereby providing insights into enhancing its delivery mechanisms for neuropathy treatment purposes. Recent advancements in delivery modalities, such as nanoparticles, allow for the controlled release of siRNA. More investigation is necessary to grasp the safety and efficacy of siRNA technology fully. It holds promise in transforming the treatment of diabetic neuropathy by honing in on particular genes and tackling issues such as inflammation and oxidative stress. Continuous advancements in delivery techniques have the potential to enhance patient results significantly. SiRNA targets genes in diabetic neuropathy, curbing nerve damage and pain and potentially preventing or delaying the condition. Customized treatments based on genetic variations hold promise for symptom management and enhancing quality of life.

Comparative Analysis of the Efficacy of Various Retreatment File Systems in the Removal of Gutta-Percha in Retreatment Cases and Time Taken During the Procedure: An In Vitro Cone Beam CT Study.

Background Removing gutta-percha manually can be a challenging task, especially when addressing densely packed root-filling material, particularly in cases where resin-based sealers are employed for obturation. The use of nickel-titanium (NiTi) rotary instruments not only effectively shapes the root canal but also efficiently removes the endodontic filling from the curved canal during retreatment. Hence, incorporating rotary NiTi instruments in retreatment cases can alleviate fatigue for both patients and operators. Objectives This study aims to compare the efficacy of Neo-Endo retreatment files, R-Endo retreatment files, and K and H files in the removal of endodontic filling material. Additionally, the remnants of gutta-percha in root canals are evaluated using cone beam computed tomography (CBCT). Materials and methods A total of 60 extracted first maxillary molar teeth were selected for this study. Canal preparation was conducted using the step-back method up to an apical size of 40 K-file. The obturation process involved the use of gutta-percha points and AH Plus sealer in a lateral compaction technique. Post-operative CBCT scans were taken. The samples were randomly divided according to the retreatment files used: group I included Neo-Endo retreatment files, group II included R-Endo retreatment files, and group III included conventional K-files and Hedstroem files (H-Files). The retreatment procedure was considered complete when the last instrument easily reached the working-length range and was physically clean. A stopwatch was used to record the time taken by each file to remove the obturating material. T1 represented the total time (including irrigation and change of file) required to reach the apex, while T2 indicated the complete removal of materials from the canal with the last instrument. The overall time recorded (TT) was calculated as T1 + T2. The removal process was analyzed with CBCT scans. Results The Neo-Endo retreatment files removed the filling materials better and more quickly than the other files. Conclusions Despite the presence of residual filling material in all samples, the Neo-Endo retreatment files left the least amount of residual filling material and achieved the shortest completion time.

Fabrication of Tungsten Oxide Nanowalls through HFCVD for Improved Electrochemical Detection of Methylamine.

In this study, well-defined tungsten oxide (WO3) nanowall (NW) thin films were synthesized via a controlled hot filament chemical vapor deposition (HFCVD) technique and applied for electrochemical detection of methylamine toxic substances. Herein, for the thin-film growth by HFCVD, the temperature of tungsten (W) wire was held constant at ~1450 °C and gasification was performed by heating of W wire using varied substrate temperatures ranging from 350 °C to 450 °C. At an optimized growth temperature of 400 °C, well-defined and extremely dense WO3 nanowall-like structures were developed on a Si substrate. Structural, crystallographic, and compositional characterizations confirmed that the deposited WO3 thin films possessed monoclinic crystal structures of high crystal quality. For electrochemical sensing applications, WO3 NW thin film was used as an electrode, and cyclic voltammetry (CV) and linear sweep voltammetry (LSV) were measured with a wide concentration range of 20 µM~1 mM of methylamine. The fabricated electrochemical sensor achieved a sensitivity of ~183.65 µA mM-1 cm-2, a limit of detection (LOD) of ~20 µM and a quick response time of 10 s. Thus, the fabricated electrochemical sensor exhibited promising detection of methylamine with considerable stability and reproducibility.

Nephroprotective Effect of Bergapten Against Cyclophosphamide-Mediated Renal Stress, Inflammation, and Fibrosis in Wistar Rats: Probable Role of NF-kB and TGF-ß1 Signaling Molecules.

Cyclophosphamide (CPM) is a well-established antineoplastic drug with marked clinical outcomes in various types of cancers. Despite being a promising drug, its use is associated with significant renal toxicity and often limits its use, leading to compromised clinical outcomes. Therefore, this study explored the renal protective effect of bergapten (BGP), a natural bioactive compound that showed marked antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. Till now, BGP has not been studied for its renal protective effect in an in vivo model. Animals were divided into control, toxic, BGP-3, BGP-10, and BGP Per se. The control group was treated with normal saline for 2 weeks. To the toxic group, CPM 200 mg/kg was given on day 7 as i.p. To BGP-3, 10, and Per se, BGP-3 and 10 mg/kg, ip was given 2 weeks with a single shot of CPM 200 day 7. To the Per se group, only BGP 10 mg/kg, ip was given from day 1 to day 14. After 14 days, animals were sacrificed, and kidneys were removed and studied for the markers of oxidative stress, inflammation, renal injury, renal fibrosis, and renal damage using biochemical, histopathological, and immunohistochemical studies. We found that BGP-10 effectively reversed the damage toward normal, whereas BGP-3 failed to exhibit a significant renal protective effect. We conclude that bergapten could be a potential renal protective drug, and hence, more detailed cellular molecular-based studies are needed to bring this drug from the bench to the bedside.

Nanoengineered chitosan functionalized titanium dioxide biohybrids for bacterial infections and cancer therapy.

Nanoengineered chitosan functionalized titanium dioxide biohybrids (CTiO2@NPs) were prepared with Amomum subulatum Roxb extract via one-pot green method and assessed by UV-Vis spectroscopy, XRD, SEM and EDAX analyses. As revealed by XRD pattern, the nanohybrids exhibits a rutile TiO2 crystallites around 45 nm in size. The emergence of the Ti-O-Ti bond is identified by observing a peak between 400 and 800 cm-1. A wide bandgap (4.8 eV) has been observed in CTiO2@NPs, due to the quantum confinement effects and the oxygen vacancies reveal the intriguing potential of developed nanohybrids for various applications. Surface flaws were identified by observing an emission band at 382, 437, 482, 517, and 556 nm. They also exhibit better antibacterial performances using well diffusion method against Staphylococcus aureus, Bacillus substilis, Klebsiella pneumonia, and Escherichia coli. CTiO2@NPs were discovered to have free radical scavenging activity on DPPH analysis and exhibit IC50 value as 95.80 µg/mL and standard (Vitamin C) IC50 is 87.62 µg/mL. CTiO2@NPs exhibited better anticancer properties against the osteosarcoma (MG-63) cell line. All these findings suggest that there is a forum for further useful therapeutic applications. Therefore, we claim that nano-engineered carbohydrated TiO2 phytohybrid is a promising solution for bacterial infections and bone cancer.

Current Progress and Emerging Role of Essential Oils in Drug Delivery Therapeutics.

The utilization of novel drug delivery systems loaded with essential oils has gained significant attention as a promising approach for biomedical applications in recent years. Plants possess essential oils that exhibit various medicinal properties, i.e., anti-oxidant, anti-microbial, anti- inflammatory, anti-cancer, immunomodulatory, etc., due to the presence of various phytoconstituents, including terpenes, phenols, aldehydes, ketones, alcohols, and esters. An understanding of conventional and advanced extraction techniques of Essential Oils (EOs) from several plant sources is further required before considering or loading EOs into drug delivery systems. Therefore, this article summarizes the various extraction techniques of EOs and their existing limitations. The in-built biological applications of EOs are of prerequisite importance for treating several diseases. Thus, the mechanisms of action of EOs for anti-inflammatory, anti-oxidant, anti-bacterial activities, etc., have been further explored in this article. The encapsulation of essential oils in micro or nanometric systems is an intriguing technique to render adequate stability to the thermosensitive compounds and shield them against environmental factors that might cause chemical degradation. Thus, the article further summarizes the advanced drug delivery approaches loaded with EOs and current challenges in the future outlook of EOs for biomedical applications.

Recent advances and mechanisms of microbial bioremediation of nickel from wastewater.

The global concern over emerging pollutants, characterized by their low concentrations and high toxicity, necessitates effective remediation strategies. Among these pollutants, pharmaceutical and personal care products, pesticides, surfactants, and persistent organic pollutants have gained significant attention. These contaminants are extensively distributed within aquatic ecosystems, posing threats to both human and aquatic physiological systems. Nickel, a valuable metal renowned for its corrosion-resistant properties, is widely utilized in various industrial processes, leading to the generation of nickel-containing waste streams, including batteries, catalysts, wastewater, and electrolyte bleed-off. Contamination of soil, water, or air by these waste materials can have adverse effects on the environment and human health. This review article focuses on the recent advancements in environmental and economic implications associated with the removal of nickel from diverse waste sources. Physicochemical technologies employed for treating different nickel-containing effluents and wastewater are discussed, alongside bioremediation techniques and the underlying mechanisms by which microorganisms facilitate nickel removal. The recovery of nickel from waste materials holds paramount importance not only from an economic standpoint but also to mitigate environmental impacts.

Ultrasound-guided percutaneous retrieval of non-radiopaque radial line using a microsnare.

Radial arterial lines are inserted in critically ill patients admitted to hospital intensive care units for continuous monitoring of their blood pressure. On removal the line can rarely become transected, potentially leading to thrombosis of the radial artery. Retrieval of the broken fragment can be achieved by open surgery, however other retrieval methods using ultrasound-guidance have been performed as they are considered safer and less invasive. We describe our technique of ultrasound-guided percutaneous retrieval of a broken non-radioopaque radial line in one patient, which involved the use of a microsnare. Under local anaesthesia and ultrasound guidance, a 6 Fr 5.5 cm short brite tip sheath was introduced into the radial artery, followed by a microsnare which was used to capture the arterial line, track the line back into the sheath and remove it uneventfully. The use of a microsnare under ultrasound-guidance is only one method to retrieve transected radial lines, with other interventional methods described in the literature. It enables a minimally invasive and safer approach to this potentially critical challenge and can help affected patients avoid open surgery to achieve the same management outcome.

Virulence traits and novel drug delivery strategies for mucormycosis post-COVID-19: a comprehensive review.

The outbreak of a fatal black fungus infection after the resurgence of the cadaverous COVID-19 has exhorted scientists worldwide to develop a nutshell by repurposing or designing new formulations to address the crisis. Patients expressing COVID-19 are more susceptible to Mucormycosis (MCR) and thus fall easy prey to decease accounting for this global threat. Their mortality rates range around 32-70% depending on the organs affected and grow even higher despite the treatment. The many contemporary recommendations strongly advise using liposomal amphotericin B and surgery as first-line therapy whenever practicable. MCR is a dangerous infection that requires an antifungal drug administration on appropriate prescription, typically one of the following: Amphotericin B, Posaconazole, or Isavuconazole since the fungi that cause MCR are resistant to other medications like fluconazole, voriconazole, and echinocandins. Amphotericin B and Posaconazole are administered through veins (intravenously), and isavuconazole by mouth (orally). From last several years so many compounds are developed against invasive fungal disease but only few of them are able to induce effective treatment against the micorals. Adjuvant medicines, more particularly, are difficult to assess without prospective randomized controlled investigations, which are challenging to conduct given the lower incidence and higher mortality from Mucormycosis. The present analysis provides insight into pathogenesis, epidemiology, clinical manifestations, underlying fungal virulence, and growth mechanisms. In addition, current therapy for MCR in Post Covid-19 individuals includes conventional and novel nano-based advanced management systems for procuring against deadly fungal infection. The study urges involving nanomedicine to prevent fungal growth at the commencement of infection, delay the progression, and mitigate fatality risk.

Addressing the resurgence of global monkeypox (Mpox) through advanced drug delivery platforms.

Monkeypox (Mpox) is a transmissible infection induced by the Monkeypox virus (a double-stranded DNA virus), recognised under the family orthopoxvirus genus. Monkeypox, like endemic diseases, is a substantial concern worldwide; thus, comprehending the pathogenesis and mutagenesis of amino acids is indispensable to combat the infection. According to the World Health Organization's report, about 89 thousand cases with 160 mortalities have been reported from 114 countries worldwide. The conventional orthopoxvirus vaccines developed on live attenuated viruses exempted any clinical validation from combating monkeypox due to inadequate immunogenicity, toxicity, instability, and multiple doses. Therefore, novel drug delivery systems come into the conception with high biological and mechanical characteristics to address the resurgence of Global Monkeypox. The edges of metallic biomaterials, novel molecules, and vaccine development in targeted therapy increase the modulation of the immune response and blockage of host-virus interaction, with enhanced stability for the antigens. Thus, this review strives to comprehend the viral cell pathogenesis concerning amino acid mutagenesis and current epidemiological standards of the Monkeypox disease across the globe. Furthermore, the review also recapitulates the various clinical challenges, current therapies, and progressive nanomedicine utilisation in the Monkeypox outbreak reinforced by various clinical trial reports. The contemporary challenges of novel drug delivery systems in Monkeypox treatment cannot be overlooked, and thus, authors have outlined the future strategies to develop successful nanomedicine to combat monkeypox. Future pandemics are inevitable but can be satisfactorily handled if we comprehend the crises, innovate, and develop cutting-edge technologies, especially by delving into frontiers like nanotechnology.

Two Decadal Experiences in Managing Combined Obstetric Vesicovaginal and Rectovaginal Fistulas: A Study From Northern Indian Tertiary Hospital.

INTRODUCTION: A retrospective study of 28 patients with obstetric combined vesicovaginal fistula (VVF) and rectovaginal fistula (RVF) treated at our centre throughout the last two decades (2002 to 2022) has been conducted. MATERIAL AND METHOD: In 12 patients, a preoperative diverting colostomy was performed. Six patients had single-stage surgery (both VVF and RVF repair in the same operation) of which two cases required transabdominal repair and four required transvaginal repair. RESULT: All single-stage repairs (n=6) were successful in curing urine and faecal incontinence. In 22 patients, VVF was corrected initially via the transvaginal method with Martius flap interposition, followed by RVF repair three months later. In 2/22 patients, there was a leak after RVF repair; therefore, proximal diverting colostomy was performed, and RVF repair was repeated after six months. CONCLUSION: All cases had effective VVF and RVF repairs, and both urine and faecal incontinence were completely cured. This study suggests the collaborative engagement of a urologist and a surgical gastroenterologist results in an advantageous outcome for the surgical treatment of these intricate obstetric fistulas.

An Overview of 1,2,3-triazole-Containing Hybrids and Their Potential Anticholinesterase Activities.

Acetylcholine (ACh) neurotransmitter of the cholinergic system in the brain is involved in learning, memory, stress responses, and cognitive functioning. It is hydrolyzed into choline and acetic acid by two key cholinesterase enzymes, viz., acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A loss or degeneration of cholinergic neurons that leads to a reduction in ACh levels is considered a significant contributing factor in the development of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD). Numerous studies have shown that cholinesterase inhibitors can raise the level of ACh and, therefore, enhance people's quality of life, and, at the very least, it can temporarily lessen the symptoms of NDs. 1,2,3-triazole, a five-membered heterocyclic ring, is a privileged moiety, that is, a central scaffold, and is capable of interacting with a variety of receptors and enzymes to exhibit a broad range of important biological activities. Recently, it has been clubbed with other pharmacophoric fragments/molecules in hope of obtaining potent and selective AChE and/or BuChE inhibitors. The present updated review succinctly summarizes the different synthetic strategies used to synthesize the 1,2,3-triazole moiety. It also highlights the anticholinesterase potential of various 1,2,3-triazole di/trihybrids reported in the past seven years (2015-2022), including a rationale for hybridization and with an emphasis on their structural features for the development and optimization of cholinesterase inhibitors to treat NDs.

Biochemical features and therapeutic potential of α-Mangostin: Mechanism of action, medicinal values, and health benefits.

α-Mangostin (α-MG) is a natural xanthone obtained from the pericarps of mangosteen. It exhibits excellent potential, including anti-cancer, neuroprotective, antimicrobial, antioxidant, and anti-inflammatory properties, and induces apoptosis. α-MG controls cell proliferation by modulating signaling molecules, thus implicated in cancer therapy. It possesses incredible pharmacological features and modulates crucial cellular and molecular factors. Due to its lesser water solubility and pitiable target selectivity, α-MG has limited clinical application. As a known antioxidant, α-MG has gained significant attention from the scientific community, increasing interest in extensive technical and biomedical applications. Nanoparticle-based drug delivery systems were designed to improve the pharmacological features and efficiency of α-MG. This review is focused on recent developments on the therapeutic potential of α-MG in managing cancer and neurological diseases, with a special focus on its mechanism of action. In addition, we highlighted biochemical and pharmacological features, metabolism, functions, anti-inflammatory, antioxidant effects and pre-clinical applications of α-MG.

Association of mutation and expression of the brother of the regulator of imprinted sites (BORIS) gene with breast cancer progression.

INTRODUCTION: The BORIS, 11 zinc-finger transcription factors, is a member of the cancer-testis antigen (CTA) family. It is mapped to chromosome number 20q13.2 and this region is genetically linked to the early onset of breast cancer. The current study analyzed the correlation between BORIS mutations and the expression of the protein in breast cancer cases. MATERIALS AND METHODS: A population-based study including a total of 155 breast cancer tissue samples and an equal number of normal adjacent tissues from Indian female breast cancer patients was carried out. Mutations of the BORIS gene were detected by polymerase chain reaction-single standard confirmation polymorphisms (PCR-SSCP) and automated DNA sequencing and by immunohistochemistry for BORIS protein expression were performed. The observed findings were correlated with several clinicopathological parameters to find out the clinical relevance of associations. RESULTS: Of all the cases 16.12% (25/155) showed mutations in the BORIS gene. The observed mutations present on codon 329 are missense, leading to Val> Ile (G>A) change on exon 5 of the BORIS gene. A significant association was observed between mutations of the BORIS gene and some clinicopathological features like nodal status (p = 0.013), estrogen receptor (ER) expression (p = 0.008), progesterone receptor (PR) expression (p = 0.039), clinical stage (p = 0.010) and menopausal status (p = 0.023). The protein expression analysis showed 20.64% (32/155) samples showing low or no expression (+), 34.19% (53/155) with moderate expression (++), and 45.17% (70/155) showing high expression (+++) of BORIS protein. A significant association was observed between the expression of BORIS protein and clinicopathological features like clinical stage (p = 0.013), nodal status (p = 0.049), ER expression (p = 0.039), and PR expression (p = 0.027). When mutation and protein expression were correlated in combination with clinicopathological parameters a significant association was observed in the category of high (+++) level of BORIS protein expression (p = 0.017). CONCLUSION: The BORIS mutations and high protein expression occur frequently in carcinoma of the breast suggesting their association with the onset and progression of breast carcinoma. Further, the BORIS has the potential to be used as a biomarker.

Exploring effects of Simvastatin on coagulation mediators to alleviate the advancement of high cholesterol diet triggered neurodegeneration.

The objectives of our study were to investigate the possible effect of Simvastatin in ameliorating high cholesterol diet (HCD)-induced neurodegeneration and to also investigate its possible action on coagulation mediators. In silico and in vitro studies were performed to evaluate the impact of Simvastatin on prime coagulation mediators. HCD was used to induce neuropathology in wistar rats and histopathological and immunohistochemical studies were performed to evaluate the efficacy of Simvastatin in preventing the advancement of neurodegeneration in obese rats. Biochemical analyses were used to estimate changes in lipid profile, oxidative stress, inflammatory and coagulation markers. Simvastatin showed good theoretical affinity to coagulation proteins, significantly reversed changes in inflammatory and coagulation biomarkers which were induced by HCD. Enhanced fibrinolytic activity of Simvastatin was revealed through in vitro analysis. Immunohistoanalysis showed raised level of Nrf2. Histopathological studies also supported neuroprotective potential of Simvastatin in HCD fed rats. Simvastatin demonstrated reduced hypercoagulation, enhanced fibrinolysis and reversed neurodegeneration in HCD exposed rats suggesting its potential role in preventing the progression of neurodegeneration in obesity.

Dexmedetomidine as Conduit for Non-Invasive Ventilation (NIV) Compliance in COVID-19 and Chronic Obstructive Pulmonary Disease (COPD) Patients in Intensive Care Unit (ICU) Setting: Case Series.

Non-compliance to the non-invasive ventilation (NIV) mask in a distressed hypoxemic patient is not an unusual finding, especially in desaturated coronavirus disease (COVID-19) or chronic obstructive pulmonary disease (COPD) patients with respiratory distress who require ventilatory support to improve oxygenation. Failure to achieve success with the non-invasive ventilatory support with the tight-fitting mask led to emergent endotracheal intubation. This was in view to avert consequences such as severe hypoxemia and subsequent cardiac arrest.  Sedation is an important component of ICU management for noninvasive mechanical ventilation to improve NIV compliance/tolerance. Including the various sedatives used, such as fentanyl, propofol, or midazolam, the most suitable agent to be used as a primary/sole sedative still remains unclear. Dexmedetomidine providing analgosedation without significant respiratory depression facilitates better tolerance of NIV mask application. This case series is a retrospective analysis of patients in whom dexmedetomidine bolus followed by infusion was observed to facilitate compliance to NIV with the tight-fitting mask. Herein, a case summary of six patients with acute respiratory distress who were dyspnoic, agitated have severe hypoxemia were put on NIV with dexmedetomidine infusion is being reported. They were extremely uncooperative as their RASS score (Richmond Agitation-Sedation score) was + 1 to +3, not allowing the application of the NIV mask. Due to their poor compliance with to use of the NIV mask, proper ventilation could not be achieved. Dexmedetomidine infusion (0.3 to 0.4 mcg/kg/hr) was used after a bolus dose (0.2-0.3 mcg/kg). The RASS Score of our patients was +2 or +3 before this intervention which became -1 or -2 after including dexmedetomidine in the treatment protocol. The low dose dexmedetomidine bolus and infusion thereafter showed to improve the patient's acceptance of the device. Oxygen therapy with this was shown to improve patient oxygenation by allowing the acceptance of the tight-fitting NIV face mask. In conclusion, this case series serves as evidence of the use of dexmedetomidine as an effective therapy to calm the agitated desaturated patient, thereby facilitating non-invasive ventilation in COVID-19 and COPD patients and promoting better oxygenation. This may, in turn, avoid endotracheal intubation for invasive ventilation and the associated complications.