Cu-Catalyzed Oxidative C(sp2)-H Cycloetherification of o-Alkenyl Arenols for the Preparation of Fused Furans.

A practically efficient, copper-catalyzed approach for the synthesis of functionally embellished indeno-naphthofurans is developed from 1-(1H-inden-3-yl)naphthalen-2-ols. This intramolecular cycloetherification proceeds via C(sp2)-H oxygenation (C-H bond breaking and C-O bond forming), which enables the atom-economical synthesis of poly fused furans in high yields with large substrate diversity in the open air.

Cu(OTf)2/HFIP catalyzed regioselective cycloisomerization of indole-C3-functionalized alkynols to carbazoles.

We report here a simple and atom economic cycloisomerization reaction of indole-tethered alkynols for constructing diverse carbazoles using Cu(OTf)2/HFIP as the excellent promoter system. The reaction proceeds through a one-pot, domino process of spiro cyclization and 1,2-migration followed by aromatization to deliver carbazoles.

Oxidative Cleavage of Csp3-Csp2 and Csp3-H Bonds with KOtBu: Highly Robust and Practical Synthesis of Diaryl/(het-Ar) Ketones.

Herein, we report an efficient and practical approach for synthesizing diaryl(het) ketones from R-CO-CHR-Ar through a simultaneous oxidative cleavage of C-C and C-H bonds using KOtBu. This method enables synthesizing a variety of unsymmetrical and symmetrical (hetero)aryl ketones in excellent yields, which are otherwise difficult to make. Besides, we synthesized natural products using this method.

Endovascular aneurysm repair conversion is an increasingly common indication for open abdominal aortic aneurysm repair.

OBJECTIVE: Although endovascular aneurysm repair (EVAR) reintervention is common, conversion to open repair (EVAR-c) occurs less frequently but can be associated with significant technical complexity and perioperative risk. There is a paucity of data highlighting the evolution of periprocedural results surrounding EVAR-c and change in practice patterns, especially for referral centers that increasingly manage EVAR failures. The purpose of this analysis was to perform a temporal analysis of our EVAR-c experience and describe changes in patient selection, operative details, and outcomes. METHODS: A retrospective single-center review of all open abdominal aortic aneurysm repairs was performed (2002-2019), and EVAR-c procedures were subsequently analyzed. EVAR-c patients (n = 184) were categorized into two different eras (2002-2009, n = 21; 2010-2019, n = 163) for comparison. Logistic regression and Cox proportional hazards modeling were used for risk-adjusted comparisons. RESULTS: A significant increase in EVAR-c as an indication for any type of open aneurysm repair was detected (9% to 27%; P < .001). Among EVAR-c patients, no change in age or individual comorbidities was evident (mean age, 71 ± 9 years); however, the proportion of female patients (P = .01) and American Society of Anesthesiologists classification >3 declined (P = .05). There was no difference in prevalence (50% vs 43%; P = .6) or number (median, 1.5 [interquartile range (IQR), 0-5]) of preadmission EVAR reinterventions; however, time to reintervention decreased (median, 23 [IQR, 6-34] months vs 0 [IQR, 0-22] months; P = .005). In contrast, time to EVAR-c significantly increased (median, 16 [IQR, 9-39] months vs 48 [IQR, 20-83] months; P = .008). No difference in frequency of nonelective presentation (mean, 52%; P = .9] or indication was identified, but a trend toward increasing mycotic EVAR-c was observed (5% vs 15%; P = .09). Use of retroperitoneal exposure (14% vs 77%; P < .0001), suprarenal cross-clamp application (6286%; P = .04), and visceral-ischemia time (median, 0 [IQR, 0-11] minutes vs 5 [IQR, 0-20] minutes; P = .05) all increased. In contrast, estimated blood loss (P trend = .03) and procedure time (P = .008) decreased. The unadjusted elective 30-day mortality rate improved but did not reach statistical significance (elective, 10% vs 5%; P = .5) with no change for non-elective operations (18% vs 16%; P = .9). However, a significantly decreased risk of complications was evident (odds ratio, 0.88; 95% confidence interval, .8-.9; P = .01). One- and 3-year survival was similar over time. CONCLUSIONS: EVAR-c is now a common indication for open abdominal aortic aneurysm repair. Patients frequently present nonelectively and at increasingly later intervals after their index EVAR. Despite increasing technical complexity, decreased complication risk and comparable survival can be anticipated when patients are managed at a high-volume aortic referral center.

Outcomes of gynecologic cancer surgery during the COVID-19 pandemic: an international, multicenter, prospective CovidSurg-Gynecologic Oncology Cancer study.

BACKGROUND: The CovidSurg-Cancer Consortium aimed to explore the impact of COVID-19 in surgical patients and services for solid cancers at the start of the pandemic. The CovidSurg-Gynecologic Oncology Cancer subgroup was particularly concerned about the magnitude of adverse outcomes caused by the disrupted surgical gynecologic cancer care during the COVID-19 pandemic, which are currently unclear. OBJECTIVE: This study aimed to evaluate the changes in care and short-term outcomes of surgical patients with gynecologic cancers during the COVID-19 pandemic. We hypothesized that the COVID-19 pandemic had led to a delay in surgical cancer care, especially in patients who required more extensive surgery, and such delay had an impact on cancer outcomes. STUDY DESIGN: This was a multicenter, international, prospective cohort study. Consecutive patients with gynecologic cancers who were initially planned for nonpalliative surgery, were recruited from the date of first COVID-19-related admission in each participating center for 3 months. The follow-up period was 3 months from the time of the multidisciplinary tumor board decision to operate. The primary outcome of this analysis is the incidence of pandemic-related changes in care. The secondary outcomes included 30-day perioperative mortality and morbidity and a composite outcome of unresectable disease or disease progression, emergency surgery, and death. RESULTS: We included 3973 patients (3784 operated and 189 nonoperated) from 227 centers in 52 countries and 7 world regions who were initially planned to have cancer surgery. In 20.7% (823/3973) of the patients, the standard of care was adjusted. A significant delay (>8 weeks) was observed in 11.2% (424/3784) of patients, particularly in those with ovarian cancer (213/1355; 15.7%; P<.0001). This delay was associated with a composite of adverse outcomes, including disease progression and death (95/424; 22.4% vs 601/3360; 17.9%; P=.024) compared with those who had operations within 8 weeks of tumor board decisions. One in 13 (189/2430; 7.9%) did not receive their planned operations, in whom 1 in 20 (5/189; 2.7%) died and 1 in 5 (34/189; 18%) experienced disease progression or death within 3 months of multidisciplinary team board decision for surgery. Only 22 of the 3778 surgical patients (0.6%) acquired perioperative SARS-CoV-2 infections; they had a longer postoperative stay (median 8.5 vs 4 days; P<.0001), higher predefined surgical morbidity (14/22; 63.6% vs 717/3762; 19.1%; P<.0001) and mortality (4/22; 18.2% vs 26/3762; 0.7%; P<.0001) rates than the uninfected cohort. CONCLUSION: One in 5 surgical patients with gynecologic cancer worldwide experienced management modifications during the COVID-19 pandemic. Significant adverse outcomes were observed in those with delayed or cancelled operations, and coordinated mitigating strategies are urgently needed.

FARGO-360: a multi-disciplinary survey of practice and perspectives on provision of care for patients with frailty presenting with gynecological cancers in the UK and Ireland.

OBJECTIVES: Frailty has been associated with worse cancer-related outcomes for people with gynecological cancers. However, the lack of clear guidance on how to assess and modify frailty prior to instigating active treatments has the potential to lead to large variations in practice and outcomes. This study aimed to evaluate current practice and perspectives of healthcare practitioners on the provision of care for patients with frailty and a gynecological cancer. METHODS: Data were collected via a questionnaire-based survey distributed by the Audit and Research in Gynecological Oncology (ARGO) collaborative to healthcare professionals who identified as working with patients with gynecological malignancies in the United Kingdom (UK) or Ireland. Study data were collected using REDCap software hosted at the University of Manchester. Responses were collected over a 16 week period between January and April 2021. RESULTS: A total of 206 healthcare professionals (30 anesthetists (14.6%), 30 pre-operative nurses (14.6%), 51 surgeons (24.8%), 34 cancer specialist nurses (16.5%), 21 medical/clinical oncologists (10.2%), 25 physiotherapists/occupational therapists (12.1%) and 15 dieticians (7.3%)) completed the survey. The respondents worked at 19 hospital trusts across the UK and Ireland. Frailty scoring was not routinely performed in 63% of care settings, yet the majority of practitioners reported modifying their practice when providing and deciding on care for patients with frailty. Only 16% of organizations surveyed had a dedicated pathway for assessment and management of patients with frailty. A total of 37% of respondents reported access to prehabilitation services, 79% to enhanced recovery, and 27% to community rehabilitation teams. CONCLUSION: Practitioners from all groups surveyed considered that appropriate training, dedicated pathways for optimization, frailty specific performance indicators and evidence that frailty scoring had an impact on clinical outcomes and patient experience could all help to improve care for frail patients.

Metabolomic Profiling for Diagnosis and Prognostication in Surgery: A Scoping Review.

OBJECTIVE: This review assimilates and critically evaluates available literature regarding the use of metabolomic profiling in surgical decision-making. BACKGROUND: Metabolomic profiling is performed by nuclear magnetic resonance spectroscopy or mass spectrometry of biofluids and tissues to quantify biomarkers (ie, sugars, amino acids, and lipids), producing diagnostic and prognostic information that has been applied among patients with cardiovascular disease, inflammatory bowel disease, cancer, and solid organ transplants. METHODS: PubMed was searched from 1995 to 2019 to identify studies investigating metabolomic profiling of surgical patients. Articles were included and assimilated into relevant categories per PRISMA-ScR guidelines. Results were summarized with descriptive analytical methods. RESULTS: Forty-seven studies were included, most of which were retrospective studies with small sample sizes using various combinations of analytic techniques and types of biofluids and tissues. Results suggest that metabolomic profiling has the potential to effectively screen for surgical diseases, suggest diagnoses, and predict outcomes such as postoperative complications and disease recurrence. Major barriers to clinical adoption include a lack of high-level evidence from prospective studies, heterogeneity in study design regarding tissue and biofluid procurement and analytical methods, and the absence of large, multicenter metabolome databases to facilitate systematic investigation of the efficacy, reproducibility, and generalizability of metabolomic profiling diagnoses and prognoses. CONCLUSIONS: Metabolomic profiling research would benefit from standardization of study design and analytic approaches. As technologies improve and knowledge garnered from research accumulates, metabolomic profiling has the potential to provide personalized diagnostic and prognostic information to support surgical decision-making from preoperative to postdischarge phases of care.

Effect of ischemia-reperfusion on outcomes after open mesenteric bypass for chronic mesenteric ischemia.

OBJECTIVE: Significant physiologic perturbations can occur in patients with chronic mesenteric ischemia (CMI) undergoing open mesenteric bypass (OMB). These events have frequently been attributed to ischemia-reperfusion events and have been directly implicated in the occurrence of multiple organ dysfunction (MOD). Scoring systems (MOD score [MODS] and sequential organ failure assessment [SOFA]) have been derived within the critical care field to provide a composite metric for these pathophysiologic changes. The purpose of the present study was to describe the early pathophysiologic changes that occur after OMB for CMI and determine whether these are predictive of the outcomes. METHODS: Patients with CMI who had undergone elective OMB from 2002 to 2018 at a single institution were reviewed. Changes in the hemodynamic, pulmonary, hepatic, renal, and hematologic parameters in the first 96 hours postoperatively were analyzed. The MODSs and SOFA scores were calculated. Cox regression was used to determine the association of the MODSs and SOFA scores with the outcomes. RESULTS: The use of OMB was analyzed for 72 patients (age, 66 ± 11 years; 68% women; body mass index, 23.8 ± 6 kg/m2; 48 ± 34-lb weight loss in 59%). Previous mesenteric stent placement or bypass had been performed in 39% [stenting in 21; bypass in 8; (one patient had both)]. An antegrade configuration (93%) was most common (retrograde configuration, 7%), with revascularization of the superior mesenteric artery/celiac vessels in 85% (superior mesenteric artery only in 15%). Postoperative pathophysiologic and metabolic changes were common, and the mean MODSs and SOFA scores were 3.6 ± 2.4 (range, 1-10) and 4.0 ± 2.7 (range, 1-13), respectively. The median length of stay was 14 days (interquartile range, 9-21). The 30-day mortality was 4% (n = 3) and in-hospital morbidity was 53% (n = 38; gastrointestinal, 25%; infectious, 22%; cardiac, 18%; pulmonary, 18%; renal, 11%). The clinical follow-up period was 16 ± 20 months. The MODSs and SOFA scores correlated linearly with overall mortality (MODS: odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2-1.7; P < .01; SOFA score: OR, 1.4; 95% CI, 1.2-1.7; P < .01 per unit), with a score of ≥5 the inflection point most predictive of mortality (MODS: OR, 3.9; 95% CI, 1.6-9.9; P ≤ .01; SOFA score: OR, 2.8; 95% CI, 1.2-6.6; P = .02). The 1- and 3-year primary bypass patency and freedom from reintervention was 91% ± 5% and 83% ± 7%, respectively, with no association with the MODSs or SOFA scores. The 1- and 3-year survival was 86% ± 4% and 71% ± 6% with significantly worse outcomes for patients with higher MODSs and/or SOFA scores. CONCLUSIONS: Most CMI patients undergoing OMB will experience significant metabolic derangements resulting from sequelae of the ischemia-reperfusion phenomenon postoperatively. These can be objectively assessed in the early postoperative period using simply applied scoring systems to reliably predict the early and long-term outcomes. A derivation of the MODS and/or SOFA score after OMB for CMI can identify the most vulnerable patients at the greatest risk of mortality.

Stereoselective sulfenylation of oxindole-derived propargyl alcohols to access sulfenylated-3-alkenyloxindoles.

A Ca-catalyzed, tetrasubstituted alkenyl-sulfenylation was achieved using readily available aryl/alkyl thiols and easily prepared oxindole-derived propargyl alcohols under solvent-free conditions. The reaction proceeded with hydrogen bonding assisted regioselective α-thiolation and subsequent calcium catalyzed stereoselective alkenylation to yield E-alkenyl thioethers with high diastereoselectivity.

Design and Encapsulation of Immunomodulators onto Gold Nanoparticles in Cancer Immunotherapy.

The aim of cancer immunotherapy is to reactivate autoimmune responses to combat cancer cells. To stimulate the immune system, immunomodulators, such as adjuvants, cytokines, vaccines, and checkpoint inhibitors, are extensively designed and studied. Immunomodulators have several drawbacks, such as drug instability, limited half-life, rapid drug clearance, and uncontrolled immune responses when used directly in cancer immunotherapy. Several strategies have been used to overcome these limitations. A simple and effective approach is the loading of immunomodulators onto gold-based nanoparticles (GNPs). As gold is highly biocompatible, GNPs can be administered intravenously, which aids in increasing cancer cell permeability and retention time. Various gold nanoplatforms, including nanospheres, nanoshells, nanorods, nanocages, and nanostars have been effectively used in cancer immunotherapy. Gold nanostars (GNS) are one of the most promising GNP platforms because of their unusual star-shaped geometry, which significantly increases light absorption and provides high photon-to-heat conversion efficiency due to the plasmonic effect. As a result, GNPs are a useful vehicle for delivering antigens and adjuvants that support the immune system in killing tumor cells by facilitating or activating cytotoxic T lymphocytes. This review represents recent progress in encapsulating immunomodulators into GNPs for utility in a cancer immunotherapeutic regimen.

Chitosan Nanoparticles-Insight into Properties, Functionalization and Applications in Drug Delivery and Theranostics.

Nanotechnology-based development of drug delivery systems is an attractive area of research in formulation driven R&D laboratories that makes administration of new and complex drugs feasible. It plays a significant role in the design of novel dosage forms by attributing target specific drug delivery, controlled drug release, improved, patient friendly drug regimen and lower side effects. Polysaccharides, especially chitosan, occupy an important place and are widely used in nano drug delivery systems owing to their biocompatibility and biodegradability. This review focuses on chitosan nanoparticles and envisages to provide an insight into the chemistry, properties, drug release mechanisms, preparation techniques and the vast evolving landscape of diverse applications across disease categories leading to development of better therapeutics and superior clinical outcomes. It summarizes recent advancement in the development and utility of functionalized chitosan in anticancer therapeutics, cancer immunotherapy, theranostics and multistage delivery systems.

Synthetic Strategies of Pyrimidine-Based Scaffolds as Aurora Kinase and Polo-like Kinase Inhibitors.

The past few decades have witnessed significant progress in anticancer drug discovery. Small molecules containing heterocyclic moieties have attracted considerable interest for designing new antitumor agents. Of these, the pyrimidine ring system is found in multitude of drug structures, and being the building unit of DNA and RNA makes it an attractive scaffold for the design and development of anticancer drugs. Currently, 22 pyrimidine-containing entities are approved for clinical use as anticancer drugs by the FDA. An exhaustive literature search indicates several publications and more than 59 patents from the year 2009 onwards on pyrimidine derivatives exhibiting potent antiproliferative activity. These pyrimidine derivatives exert their activity via diverse mechanisms, one of them being inhibition of protein kinases. Aurora kinase (AURK) and polo-like kinase (PLK) are protein kinases involved in the regulation of the cell cycle. Within the numerous pyrimidine-based small molecules developed as anticancer agents, this review focuses on the pyrimidine fused heterocyclic compounds modulating the AURK and PLK proteins in different phases of clinical trials as anticancer agents. This article aims to provide a comprehensive overview of synthetic strategies for the preparation of pyrimidine derivatives and their associated biological activity on AURK/PLK. It will also present an overview of the synthesis of the heterocyclic-2-aminopyrimidine, 4-aminopyrimidine and 2,4-diaminopyrimidine scaffolds, and one of the pharmacophores in AURK/PLK inhibitors is described systematically.

Impact of Autoantibodies to Complement Components on the Disease Activity in SLE.

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a chronic multi-system autoimmune disease with varied clinical presentations. Complement components are the major players in disease pathogenesis. This retrospective cross-sectional study was aimed at assessing the role of autoantibodies to these complement components and their association disease activity in newly diagnosed SLE patients from India. METHOD: Clinically diagnosed SLE patients (n=57) classified as per 2015 ACR/SLICC revised criteria were enrolled between November 2016 to April 2017. Patients' sera were tested for C3 and C4 by nephelometry, while serum levels of factor H, factor P (properdin) as well as autoantibodies to C3, C4, factor H and factor P were detected by ELISA. GraphPad Prism Version 6.01 was used for statistical analysis. Mean, SD, SEM were calculated. Mann Whittney U-test, ANOVA, Chi-square test, Odd's Ratio were calculated. Pearson's correlation was used to study relativeness of the study parameters. RESULTS: Among the 57 SLE patients, low C3 were seen in 51% patients, low C4 in 49%, low factor H in 19% and low factor P in 49% patients. Positivity for autoantibodies against complement components, anti-C3 were seen in 42% patients, anti-C4 in 7%, anti-factor H in 19% and anti-factor P in 28% patients. Serum levels of C3 (p=0.0009), C4 (p=0.0031) and anti-C3 autoantibodies (p=0.0029) were significantly associated with ACR/SLICC 2015 scores. CONCLUSION: Hypocomplementemia was found to be associated with higher disease damage score in newly diagnosed SLE patients. This study adds novel arguments for the importance of the anti-C3 autoantibodies as a marker of SLE.

Management of periorbital hyperpigmentation: An overview of nature-based agents and alternative approaches.

Periorbital hyperpigmentation (POH) is a common dermatological condition that presents as dark periorbital area beneath the lower eyelids, and it is commonly found in females belonging to the age group of 16 to 45 years. The data presented in this review include studies conducted on patients with a clinical/histological diagnosis of POH or melasma. Many diverse topical depigmenting agents comprising an array of naturally obtained actives such as arabinoxylans, α-arbutin, asiaticoside, azelaic acid, beta-carotene, boswellic acid, caffeine, chrysin, curcumin, cyanidin-3-glucoside, d-glucoronic acid, dihydrochalcone, dipalmitoyl-hydroxyprolene, fucoxanthin, genistein, glabridin, b-glucogallin, hyaluronic acid, lactic acid, lycopene, niacinamide, pycnogenol, retinol, salidroside, and xymenynic acid demonstrated significant benefits in the management of POH. An exhaustive literature search revealed that other techniques such as blepharoplasty, carboxytherapy, calcium hydroxylapatite fillers, tear trough implant, Q-switched ruby laser, medicated tattoo, fat transfer, micro-needling, chemical peels, nitrogen plasma skin regeneration, intense pulsed light, and radiofrequency have been evaluated and reported to be beneficial in the treatment of POH. The use of topical depigmenting agents is the most widely reported method in the clinical management of POH. Of these, α-arbutin, caffeine, cyanidin-3-glucoside, and dihydrochalcone are reported to exhibit significant benefits. Combination products containing a blend of actives are reported to be better than single active containing products. This review aims to provide a comprehensive perspective on the role of several topical actives in the modulation of melanin and tyrosinase biosynthesis pathway involved in the complex pathophysiology of POH. It also presents the advantages of combination products and other alternative therapies used in the management of POH.

Are trainees working in obstetrics and gynecology confident and competent in the care of frail gynecological oncology patients?

INTRODUCTION: Older patients undergoing cancer surgery are at increased risk of post-operative complications, prolonged hospital stay, and mortality. Identification of frailty can help predict patients at high risk of peri-operative complications and allow a collaborative, multidisciplinary team approach to their care. A survey was conducted to assess the confidence and knowledge of trainees in obstetrics and gynecology regarding identification and management of peri-operative issues encountered in frail gynecological oncology patients. METHODS: A web-based survey was distributed via the Audit and Research in Gynaecological Oncology (ARGO) collaborative and UK Audit and Research Collaborative in Obstetrics and Gynaecology (UKARCOG) . The survey on the management of frail peri-operative patients was disseminated to doctors-in-training (trainees) working in obstetrics and gynecology in the United Kingdom (UK) and Ireland. Specialty (ST1-7), subspecialty, and general practice trainees, non-training grade doctors, and foundation year doctors currently working in obstetrics and gynecology were eligible. Consultants were excluded. Study data were collected using REDCAP software hosted at the University of Manchester. Responses were collected over a 6-week period between January and February 2020. RESULTS: Of the 666 trainees who participated, 67% (425/666) reported inadequate training in peri-operative management of frail patients. Validated frailty assessment tools were used by only 9% (59/638) of trainees and less than 1% (4/613) were able to correctly identify all the diagnostic features of frailty. Common misconceptions included the use of chronological age and gender in frailty assessments. The majority of trainees (76.5%, 448/586) correctly answered a series of questions relating to mental capacity; however, only 6% (36/606) were able to correctly identify all three diagnostic features of delirium. A total of 87% (495/571) of trainees supported closer collaboration with geriatricians and a multidisciplinary approach. CONCLUSIONS: Obstetrics and gynecology trainees reported inadequate training in the peri-operative care of frail gynecological oncology patients, and overwhelmingly favored input from geriatricians. Routine use of validated frailty assessment tools may aid diagnosis of frailty in the peri-operative setting. There is an unmet need for formal education in the management of frail surgical patients within the UK and Irish obstetrics and gynecology curriculum.

An unexpected thermal-ring-rearrangement of benzochromenes to inden-3-yl-naphthols with pTsOH.

Described here is the first report of an unexpected thermal-ring rearrangement (TRR) of benzochromenes to indene derivatives promoted by pTsOH. This cascade ring-rearrangement proceeds through the protonation of benzochromenes by an acid catalyst followed by ring-opening and ring-closure by an intramolecular Friedel-Crafts cyclization to provide a new bicyclic framework, inden-3-yl-naphthols bearing a quaternary center, which also exhibited atropisomerism. Regioselectivity, broad substrate scope, high yields, solvent-free conditions and atom economy are the additional high points of this ring-rearrangement.

Intranasal Eutectic Powder of Zolmitriptan with Enhanced Bioavailability in the Rat Brain.

Intranasal administration can potentially deliver drugs to the brain because of the proximity of the delivery site to the olfactory lobe. We prepared triturates of micronized or crystalline zolmitriptan with a GRAS substance, nicotinamide, to form a eutectic. We characterized the formulation using differential scanning calorimetry, powder X-ray diffraction, and FTIR spectroscopy to confirm its eutectic nature and generated a phase diagram. The eutectic formulation was aerosolized using an in-house insufflator into the nares of rats. Groups of rats received zolmitriptan intravenously or intranasally, or intranasal eutectic formulation. Zolmitriptan was estimated in the olfactory lobe, cerebral cortex, cerebellum, and blood plasma at different time-points by LC-MS. Pharmacokinetics in these tissues indicated the superiority of the intranasal eutectic formulation for brain targeting when compared with results of IV solution and intranasal pure zolmitriptan powder. Enhancement of nose-to-brain transport is likely to have resulted from more rapid dissolution of the eutectic as compared to pure drug.

Managing dyslipidaemia in young adults.

Indians have early onset atherosclerotic cardiovascular disease and acquire the risk factors at a younger age, and hence we need to aggressively address the management of dyslipidemia in the young. Cholesterol levels early in life will influence the development of atherosclerosis. Young atherosclerotic cardiovascular disease (ASCVD) patients (18-40 yrs) should receive lipid-lowering drugs to reduce LDL-C<55 mg. Due to the asymptomatic nature of dyslipidemia, early screening will enable the implementation of management strategies which will decrease future cardiovascular events. In this review, we will provide insights into identifying and managing dyslipidemia in the 18-40 years age group (young adults). It is suggested that early detection and more aggressive management of dyslipidemia in young adults with or without risk factors like diabetes, hypertension, tobacco and central obesity, might reduce the risk of CV events occurring later in life. Although lifestyle modification is the mainstay of treatment (dietary recommendations, exercise, tobacco cessation, weight reduction, etc.) but in certain young adults we suggest use of statins in low dose or non-statin drugs if they have associated risk factors, LDL-C >160 mg or a high coronary calcium score. Young adults who are carriers of FH gene should receive aggressive lifestyle modification and appropriate antilipidemic therapy.

Recent Advances in Biomedical Applications of Mannans and Xylans.

Plant-based phytochemicals, including flavonoids, alkaloids, tannins, saponins, and other metabolites, have attracted considerable attention due to their central role in synthesizing nanomaterials with various biomedical applications. Hemicelluloses are the second most abundant among naturally occurring heteropolymers, accounting for one-third of all plant constituents. In particular, xylans, mannans, and arabinoxylans are structured polysaccharides derived from hemicellulose. Mannans and xylans are characterized by their linear configuration of ß-1,4-linked mannose and xylose units, respectively. At the same time, arabinoxylan is a copolymer of arabinose and xylose found predominantly in secondary cell walls of seeds, dicotyledons, grasses, and cereal tissues. Their widespread use in tissue engineering, drug delivery, and gene delivery is based on their properties, such as cell adhesiveness, cost-effectiveness, high biocompatibility, biodegradability, and low immunogenicity. Moreover, it can be easily functionalized, which expands their potential applications and provides them with structural diversity. This review comprehensively addresses recent advances in the field of biomedical applications. It explores the potential prospects for exploiting the capabilities of mannans and xylans in drug delivery, gene delivery, and tissue engineering.

Identification of potential focal adhesion kinase (FAK) inhibitors: a molecular modeling approach.

Focal adhesion kinase (FAK) is an enzyme of paramount importance as it is involved in several critical roles, which are linked to proliferation of cancer cells. FAK is quintessential for cancer cell mitigation, adhesion and survival, downregulation of which interferes with the growth of cancer cells. The expression of FAK is elevated in breast cancer, hepatocellular carcinomas, neuroblastoma cells, demonstrating the need for FAK inhibitors as a potential treatment. Based on an in silico drug screen, the study aimed to identify potential FAK inhibitors. 3180 molecules retrieved from the Zinc database comprising biogenic molecules, FDA-approved drugs and compounds in clinical trials were screened against the FAK enzyme (PDB:2ETM). The XP docking study of the best 51 ligands revealed that ZINC02033589 (Silymarin) showed good binding to FAK with -10.97 kcal/mol dock score followed by ZINC00518397 with -8.23 kcal/mol and ZINC03831112 - 8.07 kcal/mol. The interactions of the top three ligands with FAK were further validated by molecular dynamic simulation study of 100 ns and MM-GBSA calculations. The ΔG of binding of ZINC02033589, ZINC00518397 and ZINC03831112 was found to be -59.09, -45.08 and -48.53 kcal/mol respectively. The study established the fact that among the three molecules, ZINC02033589 showed good stability and binding towards FAK. These results could usher in the development of potential FAK inhibitor entities, that could be persuaded and substantiated by the molecules identified in this study for subsequent synthetic and bioactivity research studies.Communicated by Ramaswamy H. Sarma.