Electrophotochemical Synthesis Facilitated Trifluoromethylation of Arenes Using Trifluoroacetic Acid.

The trifluoromethyl (CF3) group is an essential moiety in medicinal chemistry due to its unique physicochemical properties. While trifluoroacetic acid (TFA) is an inexpensive and easily accessible reagent, its use as a source of CF3 is highly challenging due to its high oxidation potential. In this study, we present a novel electrophotochemical approach that enables the use of TFA as the CF3 source for the selective, catalyst- and oxidant-free trifluoromethylation of (hetero)arenes. Key to our approach is the selective oxidation of TFA over arenes, generating CF3 radicals through oxidative decarboxylation. This strategy enables the sustainable and environmentally-friendly synthesis of CF3-, CF2H- and perfluoroalkyl-containing (hetero)arenes with a broad range of substrates. Importantly, our results demonstrate significantly improved chemoselectivity by light irradiation, opening up new possibilities for the synthetic and medicinal applications of TFA as an ideal yet underutilized CF3 source.

The Role of Structural Order in the Mechanism of Charge Transport across Tunnel Junctions with Various Iron-Storing Proteins.

In biomolecular electronics, the role of structural order in charge transport (CT) is poorly understood. It has been reported that the metal oxide cores of protein cages (e.g., iron oxide and ferrihydrite nanoparticles (NPs) present in ferritin and E2-LFtn, which is E2 protein engineered with an iron-binding sequence) play an important role in the mechanism of CT. At the same time, the NP core also plays a major role in the structural integrity of the proteins. This paper describes the role of structural order in CT across tunnel junctions by comparing three iron-storing proteins. They are (1) DNA binding protein from starved cells (Dps, diameter (∅) = 9 nm); (2) engineered archaeal ferritin (AfFtn-AA, ∅ = 12 nm); and (3) engineered E2 of pyruvate dehydrogenase enzyme complex (E2-LFtn, ∅ = 25 nm). Both holo-Dps and apo-Dps proteins undergo CT by coherent tunneling because their globular architecture and relative structural stability provide a coherent conduction pathway. In contrast, apo-AfFtn-AA forms a disordered structure across which charges have to tunnel incoherently, but holo-AfFtn-AA retains its globular structure and supports coherent tunneling. The large E2-LFtn always forms disordered structures across which charges incoherently tunnel regardless of the presence of the NP core. These findings highlight the importance of structural order in the mechanism of CT across biomolecular tunnel junctions.

Interplay between Myasthenia Gravis and Severe COVID-19 Infection: The Missing Links.

Singh S, Vashishtha P, Gupta N, Wadke R, Taank P. Interplay between Myasthenia Gravis and Severe COVID-19 Infection: The Missing Links. Indian J Crit Care Med 2022;26(2):248-249.

Tracheal intubation using the Airtraq video laryngoscope vs. Macintosh laryngoscope in patients with anticipated difficult intubation.

Background: Various types of laryngoscopes have been invented to ameliorate the laryngoscopic view of the glottis, in normal and difficult airway, which helps anaesthesiologists to secure the airway during anaesthesia. In this prospective study, we aimed to compare the efficacy of the Airtraq video laryngoscope (AVL) and the Macintosh curved-blade laryngoscope (MBL), by using a common clinical assessment tool in patients with modified Mallampati class III and IV. Methods: A total of 60 patients [group A (AVL) and group M (MBL)] with modified Mallampati class III and IV listed for general anaesthesia were included. Each patient was intubated with either of the laryngoscope based on the group allotted. Time taken for tracheal intubation, grade of visualisation of glottis and need for manoeuvres to optimise the glottic view were compared. Results: The degree of the glottic view during successful intubation attempt was easily appreciated in group A (p < 0.0001). Difference in the requirement of manoeuvres for optimising the laryngeal view/assisting in intubation as assessed by manoeuvre score was easily appreciated in group A (p < 0.010). Rise in heart rate and mean arterial pressure 1 and 2 min after intubation was more in group M than in group A (p < 0.0001). No event of any airway trauma, as evidenced by visible trauma to lips or oral mucosa or blood on laryngoscope, was observed with either of the laryngoscope. Conclusion: The novel AVL provides better intubation conditions with greater ease of intubation, better glottic view and lesser haemodynamic alterations during laryngoscopy than MBL.

Comparative evaluation of nebulized ketamine and its combination with dexmedetomidine as premedication for paediatric patients undergoing surgeries under general anaesthesia.

Background: Various drugs have been endorsed but no standardised premedication protocol exists for paediatric patients. Nebulised form of drug not only results in better patient acceptability but also has improved clinical effectiveness. The present study delineates and evaluates the efficacy and safety of nebulised ketamine and combination of nebulised dexmedetomidine and ketamine for premedication in paediatric patients. Methods: Prospective randomised controlled study was planned in patients, 3-10 years of age, undergoing surgeries. Patients received either nebulised ketamine (2 mg/kg) (group X, n = 23) or dexmedetomidine 1 µg/kg plus ketamine (1 mg/kg) (group Y; n = 24), 30 min before shifting inside the operation theatre. The sedation level, haemodynamic response and ill-effects were recorded for 30 min. Results: The baseline haemodynamic (HR, MAP, RR and SpO2) parameters were normal and comparable in both the groups. There was no significant variation noticed in terms of HR, MAP, RR and SpO2% in either of the groups at 15 min (p < 0.15, p < 0.20, p < 0.85, p < 0.46) and 30 min (p < 0.21, p < 0.97, p < 0.75, p < 0.61) respectively, after receiving premedication. The level of sedation in group Y (score of 4 or less) was found to be better than that achieved by group X patients (p < 0.001). Face mask acceptance was satisfactory in group Y (score of 2 or less) as compared to group X patients (p < 0.001). The parental separation was comparable in both groups (p = 0.46). Conclusion: Nebulisation is a satisfactory method of premedication for children. A combination of nebulised ketamine with a dose of 1 mg/kg and dexmedetomidine with a dose of 1 µg/kg is capable of producing a satisfactory level of sedation in a more effective manner than sedation induced by nebulised ketamine alone (2 mg/kg).

Role of Order in the Mechanism of Charge Transport across Single-Stranded and Double-Stranded DNA Monolayers in Tunnel Junctions.

Deoxyribonucleic acid (DNA) has been hypothesized to act as a molecular wire due to the presence of an extended π-stack between base pairs, but the factors that are detrimental in the mechanism of charge transport (CT) across tunnel junctions with DNA are still unclear. Here we systematically investigate CT across dense DNA monolayers in large-area biomolecular tunnel junctions to determine when intrachain or interchain CT dominates and under which conditions the mechanism of CT becomes thermally activated. In our junctions, double-stranded DNA (dsDNA) is 30-fold more conductive than single-stranded DNA (ssDNA). The main reason for this large change in conductivity is that dsDNA forms ordered monolayers where intrachain tunneling dominates, resulting in high CT rates. By varying the temperature T and the length of the DNA fragments in the junctions, which determines the tunneling distance, we reveal a complex interplay between T, the length of DNA, and structural order on the mechanism of charge transport. Both the increase in the tunneling distance and the decrease in structural order result in a change in the mechanism of CT from coherent tunneling to incoherent tunneling (hopping). Our results highlight the importance of the interplay between structural order, tunneling distance, and temperature on the CT mechanism across DNA in molecular junctions.

The energy level alignment of the ferrocene-EGaIn interface studied with photoelectron spectroscopy.

The energy level alignment after the formation of a molecular tunnel junction is often poorly understood because spectroscopy inside junctions is not possible, which hampers the rational design of functional molecular junctions and complicates the interpretation of the data generated by molecular junctions. In molecular junction platforms where the top electrode-molecule interaction is weak; one may argue that the energy level alignment can be deduced from measurements with the molecules supported by the bottom electrode (sometimes referred to as "half junctions"). This approach, however, still relies on a series of assumptions, which are challenging to address experimentally due to difficulties in studying the molecule-top electrode interaction. Herein, we describe top electrode-molecule junctions with a liquid metal alloy top electrode of EGaIn (which stands for eutectic alloy of Ga and In) interacting with well-characterised ferrocene (Fc) moieties. We deposited a ferrocene derivative on films of EGaIn, coated with its native GaOx layer, and studied the energy level alignment with photoelectron spectroscopy. Our results reveal that the electronic interaction between the Fc and GaOx/EGaIn is very weak, resembling physisorption. Therefore, investigations of "half junctions" for this system can provide valuable information regarding the energy level alignment of complete EGaIn junctions. Our results help to improve our understanding of the energy landscape in weakly coupled molecular junctions and aid to the rational design of molecular electronic devices.

Competency-based undergraduate curriculum implementation in anesthesiology-A survey-based comparison of two models of training.

BACKGROUND AND AIM: Imparting the knowledge and skills of Anesthesiology to undergraduates can be challenging. Competency Based Undergraduate (CBUG) Curriculum for the Undergraduate medical students introduced by the Medical Council of India (MCI) aims to improve the quality of the Indian Medical Graduate (IMG). The Department of Anesthesiology and Critical Care of our college redrafted the training program and brought it in-line with the CBUG Curriculum beginning February 2019. A questionnaire based survey was conducted to assess the efficacy, satisfaction levels and the perception of the students towards the new competency based curriculum. The aim was to assess the students perception of the competency based curriculum and to evaluate two slightly different approaches to the implementation of the curriculum. MATERIAL AND METHODS: Two groups of undergraduate medical students belonging to the 6th and 8th term, underwent two different models of teaching. The 8th term students had already completed their theory classes based on the older curriculum a year ago when they were in 6th term. However, their clinics and tutorials were modelled as per the new CBUG Curriculum. The current 6th term students had their first exposure to Anesthesiology and their theory, tutorials and clinics were scheduled in the same term, simulation based training was added, the operation theatre rotation was held in the mornings at 0730hrs and the intensive care unit rounds were held in the evenings. There was no difference in the theory classes taken for the two batches, however the clinics were different. After both the batches finished their rotation, they were given the survey questionnaire to assess their perception of the model of CBUG Curriculum that they were exposed to. RESULTS: The results of the survey revealed that about 80% of the students in both groups preferred that theory classes and practical training should be conducted in parallel in 6th term. About 60% students in both groups felt that early morning clinics 0800hrs were better than mid-morning clinics at 1100hrs as they get to see and do more procedures. 66%-82% students in both groups felt that the practical training in the OT, ICU and skills lab were very helpful or extremely helpful. The most important aspect of Anesthesiology rotation was "learning basic life saving skills and simulation based learning" according to 85% students in both groups. Nearly 80% students in both groups felt that the training in Anesthesiology should be allotted more time and more weightage in undergraduate training. 72% students in 6th term and 63% students in 8th term felt more confident of handling emergencies after their Anesthesiology rotation. CONCLUSION: The new curriculum was extremely well received by the students of both groups. The model used for 6th term students comprising of teaching theory and practical in the same term and having early morning clinics, was found to be superior as compared to the model used to teach 8th term students where there was a gap of one year between theory and practical teaching and the clinics were held midmorning.

Temperature-Dependent Coherent Tunneling across Graphene-Ferritin Biomolecular Junctions.

Understanding the mechanisms of charge transport (CT) across biomolecules in solid-state devices is imperative to realize biomolecular electronic devices in a predictive manner. Although it is well-accepted that biomolecule-electrode interactions play an essential role, it is often overlooked. This paper reveals the prominent role of graphene interfaces with Fe-storing proteins in the net CT across their tunnel junctions. Here, ferritin (AfFtn-AA) is adsorbed on the graphene by noncovalent amine-graphene interactions confirmed with Raman spectroscopy. In contrast to junctions with metal electrodes, graphene has a vanishing density of states toward its intrinsic Fermi level ("Dirac point"), which increases away from the Fermi level. Therefore, the amount of charge carriers is highly sensitive to temperature and electrostatic charging (induced doping), as deduced from a detailed analysis of CT as a function of temperature and iron loading. Remarkably, the temperature dependence can be fully explained within the coherent tunneling regime due to excitation of hot carriers. Graphene is not only demonstrated as an alternative platform to study CT across biomolecular tunnel junctions, but it also opens rich possibilities in employing interface electrostatics in tuning CT behavior.

Recurrent central nervous system tuberculoma with tubercular meningitis: Swerving from asymptomatic disease to severe form.

Tuberculosis (TB) is known for its varied presentation and complications, the most dreaded complication being central nervous system (CNS) TB which includes tuberculoma. We present a case report of an asymptomatic recurrent case of CNS tuberculoma requiring multiple surgeries and prolonged critical care management.

Role Of Magnetic Resonance Spectroscopy (MRS) In Various Ring Enhancing Lesions In Brain

Aim and objective:To study the role of MR spectroscopy in the evaluation and differential diagnosis of various ring enhancing lesions in the brain with multi-voxel proton MR spectroscopy. Materials and methods: It is the prospective observational study carried out on 42 patients from June 2016 to Aug 2018 at Department of Radiodiagnosis at AVBRH, DMIMS, Sawangi, Wardha. Appropriate MRI sequences with spectroscopy and multiplanar imaging has been performed on patients with intracranial ring enhancing lesions. Result and Conclusion: Total 42 patients were taken. Most common lesions seen were tuberculoma (38%) followed by brain metastasis (34%), neurocysticercosis (16%) and pyogenic brain abscess (12%). On MRS, Tuberculoma was differentiated from NCC by high Cho: Cr ratio > 1.1 and high lipid lactate peak. Special peaks like amino acids, acetate, aspartate and succinate were seen in pyogenic brain abcess while alanine and succinate were present in NCC. High choline peak and high Cho: Cr ratio were seen in brain metastases.

Recurrent herpetic stromal keratitis in mice, a model for studying human HSK.

Herpetic eye disease, termed herpetic stromal keratitis (HSK), is a potentially blinding infection of the cornea that results in over 300,000 clinical visits each year for treatment. Between 1 and 2 percent of those patients with clinical disease will experience loss of vision of the infected cornea. The vast majority of these cases are the result of reactivation of a latent infection by herpes simplex type I virus and not due to acute disease. Interestingly, the acute infection is the model most often used to study this disease. However, it was felt that a recurrent model of HSK would be more reflective of what occurs during clinical disease. The recurrent animal models for HSK have employed both rabbits and mice. The advantage of rabbits is that they experience reactivation from latency absent any known stimulus. That said, it is difficult to explore the role that many immunological factors play in recurrent HSK because the rabbit model does not have the immunological and genetic resources that the mouse has. We chose to use the mouse model for recurrent HSK because it has the advantage of there being many resources available and also we know when reactivation will occur because reactivation is induced by exposure to UV-B light. Thus far, this model has allowed those laboratories using it to define several immunological factors that are important to this disease. It has also allowed us to test both therapeutic and vaccine efficacy.