An interesting case of chronic myeloid leukemia with twists and turns.

Additional cytogenetic abnormalities (ACA) are known to crop up in Ph+ cells of chronic myeloid leukemia (CML) patients due to cytogenetic evolution. But the frequency of molecular evolution and ACA is much less in Ph- cells of CML patients and is poorly understood. We report an interesting and rare case of Ph+ CML, who progressed to B lymphoblastic crisis, achieved remission, and later developed Ph- acute myeloid leukemia (AML) with KMT2A gene rearrangement and no detectable BCR- ABL transcripts.

Perioperative analgesic efficacy and safety of erector spinae plane block in posterior cervical spine surgery-a double blinded, randomized controlled study.

BACKGROUND CONTENT: Posterior cervical spine surgery (PCSS) are typically open surgeries and entail significant postoperative pain. Current perioperative pain management in PCSS is reliant on multimodal analgesia. While perioperative epidural anesthetic infusion can be used in lumbar surgeries, this is not an option in the cervical spine. Pre-emptive regional analgesia through erector spinae plane block (ESPB) has shown significant perioperative analgesic benefits in lumbar spine surgeries. There are no such clinical studies in PCSS. PURPOSE: To assess the safety and efficacy of ultrasound-guided ESPB for perioperative analgesia in PCSS. STUDY DESIGN: Prospective, randomized controlled, double-blinded study. PATIENT SAMPLE: Eighty-six patients requiring sub-axial PCSS with or without instrumentation were randomized into two groups, those who underwent ESPB with multimodal analgesia (case) and those with only multimodal analgesia (control). OUTCOME MEASURES: Demographic and surgical data (blood loss, duration of surgery, perioperative total opioid consumption, muscle relaxants used) were assessed. Postoperatively, the surgical site pain, alertness scale, satisfaction score, time to mobilization and complications were recorded. METHODS: After anesthesia and prone position, case patients received ultrasound-guided ESPB at the T1 level using 15 ml of 0.25% bupivacaine and 8 mg Dexamethasone bilaterally while the control patients received only standard postoperative multimodal analgesia. RESULTS: There were 43 patients in each group; the two groups were identical in demographic and surgical profile. The intraoperative opioid consumption (119.53±40.35 vs. 308.6±189.78; p<.001) in mcg), muscle relaxant usage (50.00±0.00 mg vs. 59.53±3.75 mg, p<.001), surgical duration (124.77±26.63/ 156.74±37.01 min; p<.01) and intraoperative blood loss (310.47±130.73 ml vs. 429.77±148.50 ml; p<.05) were significantly less in the ESPB group. In the postoperative period, the control group's pain score was significantly higher (p<.001). The Modified Observer Alertness/Sedation Score (MOASS) score and satisfaction scores also showed significant differences between the case and control groups (p<.001). The mean time required to ambulate (sitting/walking) was statistically less in cases (15.81±6.15/20.72±4.02 h) when compared to controls (16.86±6.18/ 23.05±8.88 h; p<.001). CONCLUSION: In patients undergoing PCSS, ESPB is a safe and effective technique with better outcomes than standard multimodal analgesia alone, in terms of reduced intraoperative opioid requirements and blood loss, better postoperative analgesia and early mobilization.

NMR Studies on the Interaction of Anticancer Drug Doxorubicin with Membrane Mimetic SDS.

In the formulation of efficient drug delivery systems, it is essential to unravel the structural and dynamical aspects of the drug's interaction with biological membranes. This has been done for the anticancer drug-membrane system comprising doxorubicin hydrochloride (DOX), a water-soluble anticancer drug, and the micellar sodium dodecyl sulfate (SDS), the latter serving as a useful mimic for membrane proteins. Using a multimodal NMR approach involving 1H, 2H, and 13C as probe nuclei and through the determination of chemical shifts, spin-relaxation, nuclear Overhauser enhancements (NOE), and translational self-diffusion (SD), the binding characteristics of the DOX with SDS have been determined. The perturbation to 13C chemical shifts of SDS indicate the penetration of DOX into the SDS micelle, which is further revealed by 1H-1H NOESY and SD measurements. 2H spin-relaxation measurements and their analysis using a two-step model show DOX induced SDS micellar volume changes, which determine the correlation times involved in the DOX-SDS mobility.

Non-Fellowship regional anesthesia training and assessment: an international Delphi study on a consensus curriculum.

BACKGROUND AND OBJECTIVES: While there are several published recommendations and guidelines for trainees undertaking subspecialty Fellowships in regional anesthesia, a similar document describing a core regional anesthesia curriculum for non-fellowship trainees is less well defined. We aimed to produce an international consensus for the training and teaching of regional anesthesia that is applicable for the majority of worldwide anesthesiologists. METHODS: This anonymous, electronic Delphi study was conducted over two rounds and distributed to current and immediate past (within 5 years) directors of regional anesthesia training worldwide. The steering committee formulated an initial list of items covering nerve block techniques, learning objectives and skills assessment and volume of practice, relevant to a non-fellowship regional anesthesia curriculum. Participants scored these items in order of importance using a 10-point Likert scale, with free-text feedback. Strong consensus items were defined as highest importance (score ≥8) by ≥70% of all participants. RESULTS: 469 participants/586 invitations (80.0% response) scored in round 1, and 402/469 participants (85.7% response) scored in round 2. Participants represented 66 countries. Strong consensus was reached for 8 core peripheral and neuraxial blocks and 17 items describing learning objectives and skills assessment. Volume of practice for peripheral blocks was uniformly 16-20 blocks per anatomical region, while ≥50 neuraxial blocks were considered minimum. CONCLUSIONS: This international consensus study provides specific information for designing a non-fellowship regional anesthesia curriculum. Implementation of a standardized curriculum has benefits for patient care through improving quality of training and quality of nerve blocks.

Interaction between sodium dodecylsulfate (SDS) and pluronic L61 in aqueous medium: assessment of the nature and morphology of the formed mixed aggregates by NMR, EPR, SANS and FF-TEM measurements.

The interaction of copolymer L61 i.e., (EO)2(PO)32(EO)2 (where EO and PO are ethylene and propylene oxides, respectively) with surfactant SDS (sodium dodecylsulfate) in relation to their self-aggregation, dynamics and microstructures has been physicochemically studied in detail employing the Nuclear Magnetic Resonance (NMR), Electron Paramagnetic Resonance (EPR), Small-Angle Neutron Scattering (SANS), and Freeze-Fracture Transmission Electron Microscopy (FF-TEM) methods. The NMR self-diffusion study indicated a synergistic interaction between SDS and L61 forming L61-SDS mixed complex aggregates, and deuterium (2H) NMR pointed out the nonspherical nature of these aggregates with increasing [L61]. EPR spectral analysis of the motional parameters of 5-doxyl steraric acid (5-DSA) as a spin probe provided information on the microviscosity of the local environment of the L61-SDS complex aggregates. SANS probed the geometrical aspects of the SDS-L61 assemblies as a function of both [L61] and [SDS]. Progressive evolution of the mixed-aggregate geometries from globular to prolate ellipsoids with axial ratios ranging from 2 to 10 with increasing [L61] was found. Such morphological changes were further corroborated with the results of 2H NMR and FF-TEM measurements. The strategy of the measurements, and data analysis for a concerted conclusion have been presented.

"On Arrival Block"-Management of Upper Extremity Trauma with Resuscitation in the Operating Room.

"On Arrival Block," wherein a brachial block is given to a severely injured upper extremity as the first step of the management protocol in the main operating room, bypassing the emergency department, has been found to be a "game changer" in trauma care. Immediate pain relief on arrival builds confidence in the system, allows pain-free initial examination, facilitates use of tourniquet if there are major bleeding wounds, and allows us to obtain good radiographs without an overlap of bones, which usually happens when the radiographs are taken within a bandage. Using the "On Arrival Block" system, emergency room assessment and resuscitation is bypassed. The patient is resuscitated only once, instead of twice. This avoids much duplication of effort, wasted time, patient suffering, unnecessary costs, and mistakes generated by miscommunication between 2 resuscitation teams. This can be done only in the place where all the resuscitative equipment and drugs are available. A senior anesthesiologist and surgeon must be available. The only contraindication is the suspicion of a brachial plexus injury, which can cause the local anesthetic to seep in through the open dural sleeve and cause total spinal anesthesia. "On Arrival Block" was set up at Ganga Hospital, Coimbatore, India, during the early 90s by the anesthesiologist Ravindra Bhat and the plastic surgeon Raja Sabapathy out of necessity, who recognized its value and made it the standard of care.

Regional anesthesia in the coronavirus disease (COVID-19) pandemic: Clinical guidelines by AORA, India.

Anesthesiologists are amongst the front line warriors in this COVID-19 pandemic. We need to change our preferences and practices to reduce the spread to healthcare workers and patients in the hospital. General anesthesia involves aerosol-generating procedures while ventilating and intubating the patients. Regional anesthesia maintains respiratory functions, circumvents airway instrumentation and helps to limit viral transmission. This makes a strong case to patronize regional anaesthesia practises whenever possible. Due to various limitations of diagnostic tests available, all patients can be treated as COVID-19 positive and necessary precautions are suggested to limit the transmission. The importance of a practise advisory is to clear the mist around the dos and don'ts to ensure clarity of thoughts leading to improved safety of both patient and health care professional. We propose clinical guidelines for regional anaesthesia practices in COVID-19 positive patient posted for surgery. Furthermore, current recommendations on confirming the COVID-19 negative status is referred. These features are subject to change further with time.

Differential Modulation in Metabolites Revealed with the Improvement in the Shelf-Life of Alphonso Fruits.

Globally farmers have difficulty in extending the shelf-life of the tropical fruits due to their perishable nature. The present study aimed to assess the effect of hexanal nano-formulation treatment (NFT) on the shelf-life of Alphonso mango. Further, volatilomics was performed to explore the molecular basis of such effect. Untreated and treated fruits were sampled starting from 5th to 21st day after NFT at an interval of 4 days. Moderate changes in visual and digital colour parameters were evident from the intact and dissected fruits of NFT set compared to untreated fruits. Biochemical assays affirmed the phenotypic differences with significant changes in the colour imparting compounds like carotenoids and anthocyanins among them. Further, gas chromatography-mass spectrometry analysis revealed significant qualitative and quantitative variations in the different classes of compounds like lactones, furanones, esters, aldehydes and alcohols. Some of the key metabolites showed differential modulations among the NFT and untreated fruit sets indicating their potential role in various processes, which ultimately might have resulted in delayed ripening of the mango. Overall, this study has demonstrated the beneficial effect of hexanal and identified important metabolites with the enhanced shelf-life in Alphonso that could be useful for farmers and mango-based food/flavour industries.

Vesicle to micelle transition in the ternary mixture of L121/SDS/D2O: NMR, EPR and SANS studies.

Subtle changes in the microstructure and dynamics of the triblock copolymer L121, (ethylene oxide)5 (propylene oxide)68 (ethylene oxide)5i.e., E5P68E5, and sodium dodecylsulfate (SDS) system in aqueous medium were investigated using high-resolution nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and small-angle neutron scattering (SANS) methods. NMR self-diffusion measurements helped us to understand the nature of binding of SDS with L121, and the formation of their mixed aggregates. These results showed that even at low [SDS] (∼2 mM), the addition of L121 stabilized the dynamics of SDS. Furthermore, the increase in [SDS] resulted in progressive changes in the diffusion behavior of both SDS and L121. 13C chemical shift analysis revealed that preferential binding of L121 occurred on the SDS micelle surface. Deuterium (2H) NMR spin-relaxation data evidenced that the formed mixed aggregates were non-spherical in terms of relaxation rate changes, and slowed the dynamics. The rotational correlation times of mixed aggregates were estimated from EPR analysis. A SANS study indicated the presence of uni- and multi-lamellar vesicles of L121 at low [SDS]. The vesicles transformed to mixed L121-SDS micelles in the presence of a higher [SDS]. This was supported by the measurements of 2H NMR spin-relaxation and EPR rotational correlation times.

The learning environment in professional doctorate and postgraduate dental education: a qualitative study.

INTRODUCTION: Currently, there is a lack of studies focusing on professional doctoral students' and graduates' perceptions of their learning environment, in particular, using a qualitative approach to elicit in-depth information. This article aims to contribute to the existing body of knowledge by systematically exploring, critically analysing and getting a deeper understanding of professional doctorate dental students' and graduates' insights into effective and ineffective clinical and physical learning environment characteristics. METHODS: The study included a total of 20 participants. Participants included 16 final-year Doctor of Clinical Dentistry (DClinDent) students and four dental specialists (graduates of the DClinDent programme). Semi-structured, individual interviews were used. Participants were asked to reflect upon and describe in detail their effective and ineffective learning environment experiences. The critical incident technique was used to guide the data collection. Data were analysed using a general inductive qualitative approach. RESULTS: Learning environment characteristics which participants associated with effective learning included the following: sufficient opportunities for comprehensive treatment planning; introduction to a number of patient treatment philosophies; a sufficient number of complex cases; clinically oriented research and assignment topics; a focus on clinical training in the programme generally; a research topic of a realistic depth and breadth, suitable for their 'specialist training' degree; and a well-resourced and updated physical infrastructure. On the other hand, most participants indicated that the absence of an adequate number of clinical cases, an overemphasis on research (as opposed to clinical practice) in the DClinDent programme and an 'outdated' physical infrastructure in the dental school clinics could hamper effective clinical learning. CONCLUSION: These findings contribute to the meaningful advancement of the literature on learning environment strategies through the exploration of (and in-depth qualitative insights into) what facilitated effective learning by New Zealand professional doctorate candidates and graduates. These findings provide a starting point for reflection by international academic directors, educational developers, curriculum planners, programme managers and clinical teachers in respect of the further development of the learning environment. Although the findings from this study may not be directly transferable to all international contexts, they have the potential to contribute to the further development of theory in this area.

Physicochemical perspectives (aggregation, structure and dynamics) of interaction between pluronic (L31) and surfactant (SDS).

The influence of the water soluble non-ionic tri-block copolymer PEO-PPO-PEO [poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)] i.e., E2P16E2 (L31) on the microstructure and self-aggregation dynamics of the anionic surfactant sodium dodecylsulfate (SDS) in aqueous solution was investigated using cloud point (CP), isothermal titration calorimetry (ITC), high resolution nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and small-angle neutron scattering (SANS) measurements. CP provided the thermodynamic information on the Gibbs free energy, enthalpy, entropy and heat capacity changes pertaining to the phase separation of the system at elevated temperature. The ITC and NMR self-diffusion measurements helped to understand the nature of the binding isotherms of SDS in the presence of L31 in terms of the formation of mixed aggregates and free SDS micelles in solution. EPR analysis provided the micro-viscosity of the spin probe 5-DSA in terms of rotational correlation time. The SANS study indicated the presence of prolate ellipsoidal mixed aggregates, whose size increased with the increasing addition of L31. At a large [L31], SANS also revealed the progressive decreasing size of the ellipsoidal mixed aggregates of SDS-L31 into nearly globular forms with the increasing SDS addition. Wrapping of the spherical SDS micelles by L31 was also corroborated from (13)C NMR and SANS measurements.

Population pharmacokinetic analysis to identify the possibility of interaction between anti-cancer agents.

BACKGROUND: A number of molecularly targeted agents in oncology are tested in clinical studies in combination with conventional chemotherapy and/or radiotherapy. There is the possibility that the pharmacokinetics and dynamics of these targeted agents may be different when administered alone as against when administered in combination with other agents. AIM: The aim of this study is to understand the effects of addition of combination agents on the pharmacokinetics of a new, investigational, cyclin dependent kinase inhibitor anti-cancer drug (Compound A) using population pharmacokinetic (pop-PK) analysis. MATERIALS AND METHODS: Integrated pop-PK analysis of data obtained from multiple phase I/II studies of Compound A, given alone or in combination with other agents. RESULTS: A two compartmental model was found suitable to explain the pharmacokinetics of Compound A. No statistically significant influence of patient covariates or combination agents on the pharmacokinetic parameters of the central compartment was detected up to a significance level of 0.01. Model evaluation showed that the parameter estimates are stable and that the variability in the data was well reproduced by the model. CONCLUSIONS: This study represents the first time that a pop-PK analysis was performed in India for a targeted anti-cancer agent being developed in India. Such an analysis is useful to not only understand the influence of patient covariates and combination agents on the pharmacokinetics of a new investigational agent, but would also be valuable in the simulation of later phase clinical trials for the agent under development.

The importance of 'student voice' in dental education.

Although much published school and higher education research have established a strong conceptual foundation for eliciting student feedback, this element is relatively poorly developed in dental education research. This paper examines 'student voice' as a conceptual/theoretical framework and justification for attending to students' perspectives in dental education. The aims of this review paper were: to explore the concept of student voice, including some pragmatic considerations and key critiques of listening to student feedback; to critically analyse key debates about the importance of a research focus on student perceptions using themes from the seminal and contemporary educational literature on student voice from the school, higher and dental educational sectors; to identify gaps in the dental education literature in relation to students' perceptions of their learning, and highlight some practical implications drawn from the 'student voice' literature for dental education; and to assist dental educational researchers in developing a strong rationale for listening to student voice in dental educational institutions. This paper is intended to assist dental educational researchers in justifying future research projects which require eliciting dental student feedback/perceptions.

Improving the quality of educational strategies in postgraduate dental education using student and graduate feedback: findings from a qualitative study in New Zealand.

INTRODUCTION: Research suggests that students' perceptions should be considered in any discussion of their education. However, to date, there has been no systematic examination of New Zealand postgraduate dental students' learning processes in both the research and clinical settings. This study aimed to obtain in-depth qualitative insights into student and graduate perspectives of effective and ineffective learning experiences during their postgraduate dental education. METHODS: Data were collected in 2010 using semi-structured individual interviews. Participants included 2010 final-year students and 2009 graduates of the University of Otago Doctor of Clinical Dentistry programme. Using the Critical Incident Technique, participants were asked to describe at least one effective and one ineffective learning experience in detail. Interview transcripts were analysed using a general inductive approach. RESULTS: Broad themes which emerged included supervisory approaches, characteristics of the learning process and characteristics of the physical learning environment. The focus of this article is to report and discuss the learning processes that participants identified as promoting and precluding effective learning experiences in the clinical and research settings. Students and graduates in the study had largely similar perspectives of learning processes likely to result in effective clinical and research learning. These included self-directed and collaborative learning; timely, constructive and detailed feedback with directions for further improvement; and discreet clinical feedback. Learning processes that precluded effective learning included unsupported and isolated learning, delayed and overly critical/destructive feedback and open criticism in the clinical context. CONCLUSION: The in-depth findings of this study contribute to the scientific literature that identifies learning process characteristics which facilitate effective learning from New Zealand postgraduate students' and graduates' perspectives. Additional cross-sectional and longitudinal studies (both qualitative and quantitative) would lead to a better understanding of what constitutes effective teaching in postgraduate dental education.

Effective and ineffective supervision in postgraduate dental education: a qualitative study.

INTRODUCTION: Research suggests that students' perceptions should be considered in any discussion of their education, but there has been no systematic examination of New Zealand postgraduate dental students' learning experiences. This study aimed to obtain in-depth qualitative insights into student and graduate perceptions of effective and ineffective learning in postgraduate dental education. METHODS: Data were collected in 2010 using semi-structured individual interviews. Participants included final-year students and graduates of the University of Otago Doctor of Clinical Dentistry programme. Using the Critical Incident Technique, participants were asked to describe atleast one effective and one ineffective learning experience in detail. Interview transcripts were analysed using a general inductive approach. RESULTS: Broad themes which emerged included supervisory approaches, characteristics of the learning process, and the physical learning environment. This paper considers students' and graduates' perceptions of postgraduate supervision in dentistry as it promotes or precludes effective learning. Effective learning was associated by participants with approachable and supportive supervisory practices, and technique demonstrations accompanied by explicit explanations. Ineffective learning was associated with minimal supervisor demonstrations and guidance (particularly when beginning postgraduate study), and aggressive, discriminatory and/or culturally insensitive supervisory approaches. CONCLUSION: Participants' responses provided rich, in-depth insights into their reflections and understandings of effective and ineffective approaches to supervision as it influenced their learning in the clinical and research settings. These findings provide a starting point for the development of curriculum and supervisory practices, enhancement of supervisory and mentoring approaches, and the design of continuing education programmes for supervisors at an institutional level. Additionally, these findings might also stimulate topics for reflection and discussion amongst dental educators and administrators more broadly.

A new dinuclear biphenylene bridged copper(II) complex: DNA cleavage under hydrolytic conditions.

The dinucleating ligand, tpbpd (tetrapyridyl biphenylenediamine) forms a dicopper complex with practically no electronic coupling between the two copper (II) centres. The EPR spectrum of the complex is consistent with coordination of each copper ion to two nitrogens of the binuclear ligand. Cyclic voltammogram of the complex also reveals that the two copper (II) centres have identical ligating environment. This dimeric copper (II) complex is found to be a very efficient catalyst for the cleavage of plasmid DNA in the absence of any added cofactor. The amount of conversion of supercoiled form (Form I) of plasmid to the open circular form (Form II) depends on the concentration of the complex as well as the duration of incubation of the complex with DNA. The maximum rate of conversion of the supercoiled form to the nicked circular form at pH 7.5 in the presence of 150 microM of the complex is found to be 1.8 x 10(-3) s(-1).

DNA damage induced by a chromium(III) Schiff base complex is reversible under physiological condition.

[Cr(naphen)(H2O)(2)]+, where naphen is 1,2-bis(naphthylideneamino)ethane having the basic salen moiety, has been characterized structurally. [Cr(naphen)(H2O)(2)]+, which has an extended aromatic system and binds with calf thymus DNA (CT DNA) intercalatively, has been found to promote DNA cleavage in the presence of biological reductant such as ascorbate and oxidant like hydrogen peroxide. Results of electron paramagnetic resonance (EPR) experiments suggest involvement of hydroxyl radicals in the oxidative cleavage of DNA in the presence of the Cr(III) complex and hydrogen peroxide. The cell viability study on nicked DNA by [Cr(naphen)(H2O)(2)]+ has shown that the damage brought about to DNA could be repaired by Escherichia coli DNA repair enzymes.

New outpatient referrals to a tertiary paediatric cardiac centre: evidence of increasing workload and evolving patterns of referral.

OBJECTIVES: To assess the volume and range of diagnosis in new patients referred to paediatric cardiac outpatient clinics. METHODS: Data was collected prospectively, using a proforma completed at all outpatient clinics over a period of three months. RESULTS: There were 526 new referrals, representing an increase of almost one-fifth compared to 5 years ago. Of the referrals, 78 percent came from hospital doctors, and 22 percent from general practitioners, with 221 of those referred being infants. A heart murmur was the most common reason for referral, representing almost two-thirds of cases. In 372 patients referred (71 percent), the heart was discovered to be structurally normal. The proportion of patients with normal hearts referred by general practitioners and hospital doctors were 81 percent, and 68 percent, respectively (p less than 0.004). There was considerable variation in the pattern of referral between doctors working in different hospitals. CONCLUSION: New referrals to centres dealing with congenital cardiac malformations are increasing alarmingly, with the majority of the children referred having normal hearts. This increase in demand for specialist services has important implications for resources and training.