Dual site reactivity of indole-3-Schiff bases with S/Se/Cl substituted ketenes for stereoselective C-4 substituted indole-ß-lactams, biological evaluations, magic chloro effect and molecular docking studies.

A convenient methodology for C-4 indole-ß-lactam hybrids with chloro, sulphur and seleno substitutions through dual site reactivity of indole-3-Schiff bases towards ketenes has been developed. The reaction proceeded in a stereospecific manner with the exclusive formation of trans-ß-lactams assigned with respect to C3-H and C4-H. The synthesized novel ß-lactams have been characterized with the help of elemental analysis (CHNS) and spectroscopic techniques viz.1H NMR, 13C NMR, DEPT 135, HSQC and IR. The trans configuration was further estabilished based on X-ray crystallographic data. Examination of antibacterial properties unveiled that only derivatives 5a and 5b, featuring chloro substitution, exhibited potent activities, underscoring the emergence of the recently coined term "magic chloro effect". Molecular docking analysis provided additional support for the observed in vitro antibacterial activities of compounds 5a-b.

Safeguarding against potential injury from an eye drops bottle.

We describe a potential cause of eye injury, its concerns and ways to prevent it. The first author underwent a left cataract operation and was prescribed eye drops postoperatively. While applying one of the eye drops, he felt an object hitting the lower eyelid. A serrated plastic piece had fallen off the bottle. Had it fallen on the operated site, it might have caused serious untoward complications. Nurses, carers and patients need to be educated to remove the serrated piece from the bottle before applying eye drops. Manufacturers of eye drops should design safer bottles without such serrated pieces to prevent such eye injuries.

Combating chlorhexidine allergy in perioperative setting.

Chlorhexidine is labelled as hidden allergen as the health care professionals (HCPs) are unaware of the wide range of products containing chlorhexidine. Adverse events from chlorhexidine allergy can be reduced by appropriate perioperative management especially heeding on positive history during preoperative assessment, awareness regarding this hidden allergen, and educating HCPs on possible chlorhexidine-containing products. The regulatory agencies all over the world have issued recommendations regarding safety and risk of hypersensitivity reactions with chlorhexidine-containing products. The onus lies on HCPs to disseminate this knowledge to the stakeholders. We present a brief update to combat chlorhexidine allergy in perioperative setting.

Exclusion of Patients with Autoimmune Disease in Lung Cancer Clinical Trials.

BACKGROUND: The exclusion of patients with autoimmune disease has been a topic of cancer immunotherapy trial. This study aims to find recent trends in exclusion of autoimmune disease. METHODS: Using the website clinicaltrials.gov, we searched for clinical trials that were initiated in 2012 or later and enrolled patients with lung cancer who were treated with PD-1/PD-L1 therapy. Only trials including US locations were analyzed. RESULTS: A total of 198 trials met screening criteria in this study. There were 68 trials which had complete exclusion of any autoimmune disease in patients. In addition, 13 trials excluded active autoimmune disease and 87 trials excluded active autoimmune disease requiring treatment. The remaining 37 trials had undefined exclusion.  Studies that had larger enrollment of patients with autoimmune diseases were largely in industry. The complete exclusion of patients with autoimmune diseases has decreased recently. CONCLUSION: Exclusion of patients with active autoimmune disease requiring treatment was one of the common exclusion criteria found.  Strict exclusion of patients with autoimmune diseases has been decreasing over the years.

Tenecteplase versus alteplase before mechanical thrombectomy: experience from a US healthcare system undergoing a system-wide transition of primary thrombolytic.

BACKGROUND: Tenecteplase (TNK) is a genetically modified variant of alteplase (TPA) and has been established as a non-inferior alternative to TPA in acute ischemic stroke (AIS). Whether TNK exerts distinct benefits in large vessel occlusion (LVO) AIS is still being investigated. OBJECTIVE: To describe our first-year experience after a healthcare system-wide transition from TPA to TNK as the primary thrombolytic. METHODS: Patients with AIS who received intravenous thrombolytics between January 2020 and August 2022 were retrospectively reviewed. All patients with LVO considered for mechanical thrombectomy (MT) were included in this analysis. Spontaneous recanalization (SR) after TNK/TPA was a composite variable of reperfusion >50% of the target vessel territory on cerebral angiography or rapid, significant neurological recovery averting MT. Propensity score matching (PSM) was performed to compare SR rates between TNK and TPA. RESULTS: A total of 148 patients were identified; 51/148 (34.5%) received TNK and 97/148 (65.5%) TPA. The middle cerebral arteries M1 (60.8%) and M2 (29.7%) were the most frequent occlusion sites. Baseline demographics were comparable between TNK and TPA groups. Spontaneous recanalization was significantly more frequently observed in the TNK than in the TPA groups (unmatched: 23.5% vs 10.3%, P=0.032). PSM substantiated the observed SR rates (20% vs 10%). Symptomatic intracranial hemorrhage, 90-day mortality, and functional outcomes were similar. CONCLUSIONS: The preliminary experience from a real-world setting demonstrates the effectiveness and safety of TNK before MT. The higher spontaneous recanalization rates with TNK are striking. Additional studies are required to investigate whether TNK is superior to TPA in LVO AIS.

Twenty-first century skills teaching in anaesthesia.

The core competencies defined by the Accreditation Council for Graduate Medical Education merge under the 21st century skills. Technological advancements and globalisation have posed new requirements on all fronts. The 21st century skills are the 12 essential abilities for success in the internet age. Medical education has adapted the 21st century skills in all aspects. The 21st century skills are essential for producing relevant doctors in the age of internet and artificial intelligence. In this article, we present an example of teaching the anaesthesia basics by applying the 21st century skills.

Potential of smartphone enabled otoscopy for teleconsultation and teaching.

The smartphone enabled otoscope (SEO) provides an opportunity for telemedicine and enhancing teaching of otoscopy. We describe our preliminary experience with the use of one such inexpensive device bought from an online store. It is a simple and feasible procedure which patients can perform on themselves (or guardians on their wards) after minimal training. The resolution of the image is adequate for follow up through teleconsultation. It is also a good teaching tool as it enables the sharing of views.

Coping with uncertainties for medical students.

No abstract provided.

Perioperative Continuous Noninvasive Arterial Pressure Monitoring for Neuroendovascular Interventions: Prospective Study for Evaluation of the Vascular Unloading Technique.

BACKGROUND: Blood pressure monitoring is crucial during neuroendovascular procedures. Intraoperative hemodynamic instability is associated with complications, which underscores the importance of continuous monitoring. Although direct measurement with an intra-arterial catheter is the gold standard for determining arterial pressure, it is costly, time-consuming, and associated with complications. The novel ClearSight system offers a noninvasive technique for monitoring arterial pressure via a finger cuff. This study compared noninvasive arterial pressure measurements with the gold standard method. METHODS: Simultaneous recording of noninvasive and invasive arterial pressure was performed in patients undergoing neuroendovascular interventions. Both techniques were compared employing linear regression, Lin's correlation coefficient, Bland-Altman, and error grid analysis. RESULTS: The study enrolled 24 consecutive patients. The concordance correlation coefficient between both methods was 0.3526 (95% confidence interval [0.3134, 0.3906]) for mean arterial pressure and 0.4680 (95% confidence interval [0.4353, 0.4995]) and for systolic arterial pressure. The mean (SD) of the differences was 0.81 (17.86) mm Hg (95% limits of agreement [-52.52, 54.14]) for mean arterial pressure and 5.38 (14.64) mm Hg (95% limits of agreement [-45.12, 56.08]) for systolic arterial pressure. Error grid analysis demonstrated that the majority of measurements lie in regions with no or low risk for patients (mean arterial pressure, 71.0% and 24.4%; systolic arterial pressure, 59.2% and 25.8%). CONCLUSIONS: The ClearSight system provided accurate measurements of arterial blood pressure compared with invasive methods and within safe clinical parameters. This method may serve as a safe and reliable alternative for invasive blood pressure monitoring during neuroendovascular procedures.

Beyond border health: Infrastructural violence and the health of border abolition.

Most existing approaches to border health focus on identifying the social determinants that produce ill health and health disparities among migrants, including language barriers, documentation status, and trauma associated with migration. Attention to these kinds of problems can lead to policy and clinical changes that indeed help improve quantitatively measurable outcomes for patients. However, these approaches usually ignore the larger historical and political framework that determines the determinants - the underlying infrastructure of ill health, or what we term the infrastructural determinants of health. In this paper, we outline specific infrastructures involving race, political economy, history, and most importantly, borders themselves, that lay the foundations for border illness. We examine the plans, histories, policies, and peoples involved in building the conditions for migration, particularly out of the Northern Triangle, including forces of colonialism, US imperialism, neoliberalism, and border militarization. In place of a tacit acceptance of the modern system of borders, we argue for border abolition as a vital but underused treatment in the repertoire of medical intervention. Outlining the rights of people to stay and to move, and drawing on lessons from the prison abolition movement, we offer policies and practices towards a 'no borders' system that privileges liberatory solidarity with migrants by explicitly challenging global infrastructures that drive displacement. In doing so, we offer an emergent framework for a medical border abolition that treats both the causes and symptoms of a widespread global sickness.

Purification and identification of a surfactin biosurfactant and engine oil degradation by Bacillus velezensis KLP2016.

Engine oil used in automobiles is a threat to soil and water due to the recalcitrant properties of its hydrocarbons. It pollutes surrounding environment which affects both flora and fauna. Microbes can degrade hydrocarbons containing engine oil and utilize it as a substrate for their growth. Our results demonstrated that cell-free broth of Bacillus velezensis KLP2016 (Gram + ve, endospore forming; Accession number KY214239) recorded an emulsification index (E24%) from 52.3% to 65.7% against different organic solvents, such as benzene, pentane, cyclohexane, xylene, n-hexane, toluene and engine oil. The surface tension of the cell-free broth of B. velezensis grown in Luria-Bertani broth at 35 °C decreased from 55 to 40 mN m-1at critical micelle concentration 17.2 µg/mL. The active biosurfactant molecule of cell-free broth of Bacillus velezensis KLP2016 was purified by Dietheylaminoethyl-cellulose and size exclusion chromatography, followed by HPLC (RT = 1.130), UV-vis spectrophotometry (210 nm) and thin layer chromatography (Rf = 0.90). The molecular weight of purified biosurfactant was found to be ~ 1.0 kDa, based on Electron Spray Ionization-MS. A concentration of 1980 × 10-2 parts per million of CO2 was trapped in a KOH solution after 15 days of incubation in Luria-Bertani broth containing 1% engine oil. Our results suggest that bacterium Bacillus velezensis KLP2016 may promise a new dimension to solving the engine oil pollution problem in near future.

Comparison of PED and FRED flow diverters for posterior circulation aneurysms: a propensity score matched cohort study.

BACKGROUND: Flow diversion is a common endovascular treatment for cerebral aneurysms, but studies comparing different types of flow diverters are scarce. OBJECTIVE: To perform a propensity score matched cohort study comparing the Pipeline Embolization Device (PED) and Flow Redirection Intraluminal Device (FRED) for posterior circulation aneurysms. METHODS: Consecutive aneurysms of the posterior circulation treated at 25 neurovascular centers with either PED or FRED were collected. Propensity score matching was used to control for age, duration of follow-up imaging, adjunctive coiling, and aneurysm location, size, and morphology; previously ruptured aneurysms were excluded. The two devices were compared for the following outcomes: procedural complications, aneurysm occlusion, and functional outcome. RESULTS: A total of 375 aneurysms of the posterior circulation were treated in 369 patients. The PED was used in 285 (77.2%) and FRED in 84 (22.8%) procedures. Aneurysms treated with the PED were more commonly fusiform and larger than those treated with FRED. To account for these important differences, propensity score matching was performed resulting in 33 PED and FRED unruptured aneurysm pairs. No differences were found in occlusion status and neurologic thromboembolic or hemorrhagic complications between the two devices. The proportion of patients with favorable functional outcome was higher with FRED (100% vs 87.9%, p=0.04). CONCLUSION: Comparative analysis of PED and FRED for the treatment of unruptured posterior circulation aneurysms did not identify significant differences in aneurysm occlusion or neurologic complications. Variations in functional outcomes warrant additional investigations.

Lipopeptide(s) associated with human microbiome as potent cancer drug.

Human microbiota comprises of trillions of microbes which have evolved with and continued to live on/ within their human hosts. Different environmental factors and diet have a large impact upon human microbiota population. These microorganisms live in synergy with their hosts and are beneficial to the host in many different ways. Many microorganisms help to fight against human diseases. Cancer is one such diseases which effects a large human population often leading to death. Cancer is also one of the most fatal human diseases killing millions of people world-wide every year. Though many treatment procedures are available but none is 100 % effective in curing cancer. In this review, we seek to understand the role of human microbiota in cancer treatment. Lipopeptide(s) (LPs) produced by different microorganisms can act as efficient drug(s) against cancer. LPs are low molecular weight lipo-proteins that are also known for their anti-cancer activities. As human microbiota belongs to an environment within the host body, a drug prepared using these microorganisms will be easily accepted by the body. This novel approach of using LPs produced by human microbiota can be considered for the much needed change in cancer treatment. Therefore, it is proposed that research should focus on the host-microbe interaction which could pave the way in understanding role played by these microorganisms in cancer treatment.

Experience With the Pipeline Embolization Device for Posterior Circulations Aneurysms: A Multicenter Cohort Study.

BACKGROUND: The Pipeline Embolization Device (PED; Medtronic) has been used off-label for the treatment of challenging posterior circulation aneurysms. Data on this modality are primarily limited to small retrospective single-center series. OBJECTIVE: To assess safety and efficacy of this treatment by establishing an international, multicenter collaboration. METHODS: Consecutive posterior circulation aneurysms treated with the PED from 2012 to 2019 across 11 neurovascular centers were retrospectively reviewed. Baseline demographics, aneurysm and treatment characteristics, complications, occlusion status, and functional outcome were assessed. RESULTS: There were 149 posterior circulation aneurysms treated with PED in 146 patients. A total of 24 (16.4%) patients presented with subarachnoid hemorrhage. Most aneurysms were dissecting/blister (36.2%) in morphology, followed by saccular (35.6%) and fusiform (28.2%). The most common locations were the vertebral (51.7%) and basilar arteries (22.8%). Complete or near-complete occlusion (>90%) was achieved in 90.9% of aneurysms at a median follow-up of 12 mo. Dissecting/blister aneurysms were most likely to occlude (P = .06). Symptomatic neurologic complications occurred in 9.4% of aneurysms, associated with larger size, ruptured presentation, presentations with brain stem compression, cranial nerve palsy, or stroke. Favorable functional outcome (modified Rankin Score 0-2) was achieved in 86.2% of patients. There were 6 fatalities of which 4 occurred in aneurysmal subarachnoid hemorrhage patients. CONCLUSION: This multicenter study shows that PED for the treatment of posterior circulation is preferentially used for the treatment of fusiform and dissecting/blister aneurysm morphologies. Despite the challenges presented by these less-common morphologies, flow diversion may be performed with a neurologic complication rate of about 10% and favorable long-term aneurysm occlusion rates.

Intraoperative 3-Dimensional Rotational Angiography in Cerebrovascular Surgery: A Case Series.

OBJECTIVE: Intraoperative imaging is critical in cerebrovascular surgery to assess the technical success of the operation. This case series aimed to evaluate the safety and efficacy of 3-dimensional rotational angiogram (3D-RA) in addition to 2-dimensional intraoperative angiography (2D-IOA) during cerebrovascular surgery in the hybrid operating room. METHODS: All consecutive patients who underwent open cerebrovascular surgery and intraoperative 2D-IOA with 3D-RA in a hybrid operating room at 2 academic centers between August 2018 and December 2019 were identified from a prospectively maintained institutional database. Medical charts and operative videos including intraoperative angiography were reviewed, and clinical and angiographic outcomes assessed. RESULTS: A total of 40 cerebrovascular surgeries in 39 patients (mean age, 53 ± 13 years; 51% female) were carried out with the addition of 3D-RA to 2D-IOA in the hybrid operating room. After 3D-RA in addition to 2D-IOA, 1 (2.5%) surgical alteration occurred in an aneurysm clipping. Other procedures were not altered with the addition of 3D-RA to 2D-IOA. There were no complications from the addition of 3D-RA to 2D-IOA. CONCLUSIONS: Using a combination of 3D-RA and 2D-IOA in the hybrid operating room may enhance the likelihood of achieving an optimal result when employing microsurgical cerebrovascular surgery and avoid unanticipated incomplete outcomes, complications, and returns to the operating room. Whereas the addition of 3D-RA elucidated residual aneurysm not otherwise visualized on the 2D-IOA, in other cerebrovascular procedures studied, there was no additional value of the 3D-RA over the 2D-IOA.

Pharmacy-Mediated Antiplatelet Management Protocol Compared to One-time Platelet Function Testing Prior to Pipeline Embolization of Cerebral Aneurysms: A Propensity Score-Matched Cohort Study.

BACKGROUND: There is ongoing controversy regarding the optimal antiplatelet regimen, and extent or even need for platelet function testing surrounding Pipeline flow diverter (Medtronic Inc, Dublin, Ireland) embolization of cerebral aneurysms. OBJECTIVE: To compare a unique pharmacy-mediated antiplatelet medication management protocol to a 1-time platelet function testing strategy prior to Pipeline placement. METHODS: A retrospective review of patients with cerebral aneurysms who underwent Pipeline embolization at 2 academic institutions was performed. The first line antiplatelet regimen consisted of aspirin and clopidogrel at both institutions. At institution A, the pharmacy-mediated antiplatelet medication management protocol consisted of repeat platelet function testing using VerifyNow (Accriva Diagnostics, San Diego, California), and dosing adjustments prior to and after Pipeline placement. At institution B, a 1-time platelet function test using light transmission aggregometry was obtained prior to Pipeline placement. Both strategies were compared using propensity score matching. RESULTS: A total of 63 and 165 Pipeline embolization procedures were performed at institutions A and B, respectively. Baseline characteristics differed in aneurysm location and aneurysm maximal diameter. Propensity score matching resulted in 25 matched pairs and demonstrated that the number of procedures in which the patient was switched to an alternative platelet agent was significantly smaller at institution A. There were no differences between the sites with regard to aneurysm occlusion rate, the incidence of thromboembolic and hemorrhagic complications, and modified Rankin scale at last follow-up after propensity score matching. CONCLUSION: Pharmacy-mediated antiplatelet management using VerifyNow is a safe and efficacious alternative to a more traditional approach, and significantly reduces the need to utilize other, potentially more expensive antiplatelet agents.

A Comprehensive Review on C-3 Functionalization of ß-Lactams.

BACKGROUND: A lot of advancement has been made in the area of ß-lactams in recent times. Most of the research is targeted towards the synthesis of novel ß-lactams, their functionalization and exploring their biological potential. The C-3 functionalization of ß-lactams has continued to attract considerable interest of the scientific community due to their utility as versatile intermediates in organic synthesis and their therapeutic applications. This has led to the significant increase in efforts towards developing efficient and economic strategies for C-3 functionalized ß-lactams. OBJECTIVE: The present review aims to highlight recent advancement made in C-3 functionalization of ß - lactams. CONCLUSION: To summarize, functionalization of ß-lactams at C-3 is an essential aspect of ß-lactam chemistry in order to improve/modify its synthetic utility as well as biological potential. The C-3 carbocation equivalent method has emerged as an important and convenient strategy for C-3 functionalization of ß-lactam heterocycles which provides a wide range of ß-lactams viz. 3-alkylated ß-lactams, 3-aryl/heteroarylated ß-lactams, 3- alkoxylated ß-lactams. On the other hand, base mediated functionalization of ß-lactams via carbanion intermediate is another useful approach but their scope is limited by the requirement of stringent reaction conditions. In addition to this, organometallic reagent mediated α-alkylation of 3-halo/3-keto-ß-lactams also emerged as interesting methods for the synthesis of functionalized ß-lactams having good yields and diastereoselectivities.