Severe Diabetic Ketoacidosis with Malignant Hyperthermia Like Syndrome and Rhabdomyolysis Treated with ECMO: Unusual Severity and a Rare Occurrence.

How to cite this article: Accamma K, Shamarao S, Ram A, Devananda NS, Krishna M, Bandagi LS, et al. Severe Diabetic Ketoacidosis with Malignant Hyperthermia Like Syndrome and Rhabdomyolysis Treated with ECMO: Unusual Severity and a Rare Occurrence. Indian J Crit Care Med 2023;27(11):859-860.

Assembly of the Mitochondrial Translation Initiation Complex.

Mitochondria maintain their own translational machinery that is responsible for the synthesis of essential components of the oxidative phosphorylation system. The mammalian mitochondrial translation system differs significantly from its cytosolic and bacterial counterparts. Here, we describe detailed protocols for efficient in vitro reconstitution of the mammalian mitochondrial translation initiation complex, which can be further used for mechanistic analyses of different aspects of mitochondrial translation.

Role of Telemedicine in Diabetes Management.

INTRODUCTION: Telemedicine is a growing arena that may increase access to care for patients with diabetes. It has more relevance for rural populations or those with limited physical access to health care, for improving diabetes care. Telemedicine can also be used to offer diabetes self-education and transportation barriers for patients living in under-resourced areas or with disabilities. METHOD: "This review explores the landscape of telemedicine approaches and evidence for incorporation into general practice. RESULTS & DISCUSSION: Telehealth platforms have been shown to be both feasible and effective for health care delivery in diabetes, although there are many caveats that require tailoring to the institution, clinician, and patient population. Research in diabetes telehealth should focus next on how to increase access to patients who are known to be marginalized from traditional models of health care.

Ataluren binds to multiple protein synthesis apparatus sites and competitively inhibits release factor-dependent termination.

Genetic diseases are often caused by nonsense mutations, but only one TRID (translation readthrough inducing drug), ataluren, has been approved for clinical use. Ataluren inhibits release factor complex (RFC) termination activity, while not affecting productive binding of near-cognate ternary complex (TC, aa-tRNA.eEF1A.GTP). Here we use photoaffinity labeling to identify two sites of ataluren binding within rRNA, proximal to the decoding center (DC) and the peptidyl transfer center (PTC) of the ribosome, which are directly responsible for ataluren inhibition of termination activity. A third site, within the RFC, has as yet unclear functional consequences. Using single molecule and ensemble fluorescence assays we also demonstrate that termination proceeds via rapid RFC-dependent hydrolysis of peptidyl-tRNA followed by slow release of peptide and tRNA from the ribosome. Ataluren is an apparent competitive inhibitor of productive RFC binding, acting at or before the hydrolysis step. We propose that designing more potent TRIDs which retain ataluren's low toxicity should target areas of the RFC binding site proximal to the DC and PTC which do not overlap the TC binding site.

Origin of Intense Luminescence from Supramolecular 2D Molecular Crystals.

Luminescence enhancement in 2D molecular crystals (2D crystals) is promising for a variety of optical applications, yet the availability is limited because of unclear mechanism and inefficient design strategy of luminescence control. Herein, the room temperature phosphorescence from micron long molecular thin free-standing 2D crystals of a mono-cyclometalated Ir(III) complex designed at the water surface is reported. A large luminescence enhancement is observed from the 2D crystals at 300 K, which is comparable with the rigidified solution at 77 K suggesting room temperature phosphorescence origin of the luminescence. In situ synchrotron grazing incidence X-ray diffraction measurements determine the constituent centered rectangular unit cells with precise molecular conformation that promotes the formation of 2D crystals. The molecular crystal design leads to a reduced singlet-triplet energy gap (ΔEST ) and mixing of singlet-triplet states by spin-orbit coupling (SOC) for efficient intersystem crossing, which explains the phosphorescence origin at room temperature and luminescence enhancement. The supramolecular assembly process provides an elegant design strategy to realize room temperature phosphorescence from 2D crystals by rigid intermolecular interactions.

Femtosecond laser-induced spin dynamics in single-layer graphene/CoFeB thin films.

Graphene/ferromagnet hybrid heterostructures are important building blocks of spintronics due to the unique ability of graphene to transport spin current over unprecedented distances and possible increase in its spin-orbit coupling due to proximity and hybridization. Here, we present magnetization dynamics over a femtosecond to nanosecond timescale by employing an all-optical time-resolved magneto-optical Kerr effect technique in single-layer graphene (SLG)/CoFeB thin films with varying CoFeB thickness and compared them with reference CoFeB thin films without an SLG underlayer. Gilbert damping variation with CoFeB thickness is modelled to extract spin-mixing conductance for the SLG/CoFeB interface and isolate the two-magnon scattering contribution from spin pumping. In SLG/CoFeB, we have established an inverse relationship between ultrafast demagnetization time (τm) and the Gilbert damping parameter (α) induced by interfacial spin accumulation and pure spin-current transport via a spin pumping mechanism. This systematic study of ultrafast demagnetization in SLG/CoFeB heterostructures and its connection with magnetic damping can help to design graphene-based ultrahigh-speed spintronic devices.

Unraveling the physical properties and superparamagnetism in anti-site disorder controlled Fe2TiSn.

With an aim to control the anti-site disorder between Fe and Ti atoms in the full Heusler alloy, Fe[Formula: see text]TiSn, we substitute a small percentage of Ti at Fe site to form the Fe[Formula: see text]Ti[Formula: see text]Sn ([Formula: see text]) series. Using the incident x-rays tuned to the Fe K-edge absorption energy, we record the high resolution synchrotron x-ray diffraction profiles and unambiguously show the reduction in anti-site disorder. In particular, the Fe-Ti anti-site disorder decreases up to an excess Ti content of 0.07; further increase of Ti content leads to disorder between Ti-Sn sites. Detailed characterization vis-á-vis the excess Ti content has been carried out in terms of its thermal and electrical transport, and magnetic properties. Signatures of strong spin fluctuation are seen in all the physical properties reported here. The much disputed high value of the Sommerfeld constant has been shown to be a resultant of such strong spin fluctuations, thus ruling out the long standing controversy of heavy fermionic nature of Fe[Formula: see text]TiSn. Magnetization and the Seebeck coefficient show clear dependence on the disorder. Both dc and ac magnetic measurements reveal the low temperature superparamagnetic nature of this system, comprising of large magnetic clusters [Formula: see text]3 nm in size.

Synergistic Enhancement of Electron-Accepting and -Donating Ability of Nonconjugated Polymer Nanodot in Micellar Environment.

Understanding the fundamental electron-transfer dynamics in photoactive carbon nanoparticles (CNPs) is vitally important for their fruitful application in photovoltaics and photocatalysis. Herein, photoinduced electron transfer (PET) to and from the nonconjugated polymer nanodot (PND), a new class of luminescent CNP, has been investigated in the presence of N,N-dimethylaniline (DMA) and methyl viologen (MV2+) in homogeneous methanol and sodium dodecyl sulfate (SDS) micelles. It has been observed that both DMA and MV2+ interact with the photoexcited PND and quench the PL intensity as well as excited-state lifetime in bulk methanol. While in bulk methanol, purely diffusion-controlled PET from DMA to MV2+ via PND has been observed, the mechanism and dynamics differ significantly in SDS micelles. In contrast to homogeneous methanol medium, a distinct synergic effect has been observed in SDS micelles. The presence of both DMA and MV2+ enhances the electron-accepting and -donating abilities of PND in SDS micelles. Time-resolved photoluminescence (PL) measurements reveal that the PET process in SDS micelles is nondiffusive in nature mainly due to instantaneous electron transfer at the confined micellar surface. These results have been explained on the basis of heterogeneous microenvironments of SDS micelles which compartmentalize the donor and acceptor inside its micellar pseudo phase. The present findings provide valuable insights into the intrinsic relation between redox and PL properties of nonconjugated PND.

Direct Evidence of Intrinsic Blue Fluorescence from Oligomeric Interfaces of Human Serum Albumin.

The molecular origin behind the concentration-dependent intrinsic blue fluorescence of human serum albumin (HSA) is not known yet. This unusual blue fluorescence is believed to be a characteristic feature of amyloid-like fibrils of protein/peptide and originates due to the delocalization of peptide bond electrons through the extended hydrogen bond networks of cross-ß-sheet structure. Herein, by combining the results of spectroscopy, size exclusion chromatography, native gel electrophoresis, and confocal microscopy, we have shown that the intrinsic blue fluorescence of HSA exclusively originates from oligomeric interfaces devoid of any amyloid-like fibrillar structure. Our study suggests that this low energy fluorescence band is not due to any particular residue/sequence, but rather it is a common feature of self-assembled peptide bonds. The present findings of intrinsic blue fluorescence from oligomeric interfaces pave the way for future applications of this unique visual phenomenon for early stage detection of various protein aggregation related human diseases.

Insights into the Thermodynamics of Polymer Nanodot-Human Serum Albumin Association: A Spectroscopic and Calorimetric Approach.

With the advent of newer luminescent nanoparticles for bioimaging applications, their complex interactions with individual biomolecules need to be understood in great detail, before their direct application into cellular environments. Here, we have presented a systematic and detailed study on the interaction between luminescent polymer nanodots (PNDs) and human serum albumin (HSA) in its free and ligand-bound state with the help of spectrophotometric and calorimetric techniques. At physiological pH (pH = 7.4), PNDs quench the intrinsic fluorescence of HSA as a consequence of ground-state complex formation. The binding stoichiometry and various thermodynamic parameters have been evaluated by using isothermal titration calorimetry and the van't Hoff equation. It has been found that the association of PNDs with HSA is spontaneous (ΔG0 = -32.48 ± 1.24 kJ mol-1) and is driven by a favorable negative standard enthalpy change (ΔH0 = -52.86 ± 2.12 kJ mol-1) and an unfavorable negative standard entropy change (ΔS0 = -68.38 ± 2.96 J mol-1 K-1). These results have been explained by considering hydrogen bonding interactions between amino and hydroxyl groups (-NH2 and -OH) of PNDs and carboxylate groups (-COO-) of glutamate (Glu) and aspartate (Asp) residues of HSA. The binding constant of PNDs with HSA is estimated to be 4.90 ± 0.19 × 105 M-1. Moreover, it has been observed that warfarin-bound HSA (war-HSA) shows a significantly lower binding affinity (Kb = 1.15 ± 0.19 × 105 M-1) toward PNDs, whereas ibuprofen-bound HSA (ibu-HSA) shows a slightly lower affinity (Kb = 3.47 ± 0.13 × 105 M-1) compared with the free HSA. In addition, our results revealed that PNDs displace warfarin from site I (subdomain IIA) of HSA because of the partial unfolding of war-HSA. We hope that the present study will be helpful to understand the fundamental interactions of these biocompatible PNDs with various biological macromolecules.

Resonant excitation energy transfer from carbon dots to different sized silver nanoparticles.

The influence of size on the efficiency of the nanometal surface energy transfer (NSET) process between excited donors and different sized metal nanoparticles (NPs) is poorly explored in the literature. Here we present a systematic study by correlating the size of silver nanoparticles (Ag NPs) with the efficiency of excitation energy transfer (EET) from carbon dots (CDs) to Ag NPs. Three different sized citrate-capped Ag NPs with a mean hydrodynamic diameter of 39.91 ± 1.03, 53.12 ± 0.31 and 61.84 ± 0.77 nm have been synthesized for the present study. The estimated zeta potential of the synthesized CD is -25.45 ± 1.23 mV while that for the smallest, medium and largest sized Ag NPs are -76.24 ± 3.92, -67.60 ± 4.40, and -58.01 ± 3.10 mV, respectively. The steady-state and time-resolved PL measurements reveal a significant PL quenching of CDs as a function of Ag NP size. A control experiment with Ag NPs having a LSPR at 398 nm shows a negligible amount of PL quenching of CDs as a consequence of inadequate spectral overlap. The origin behind this PL quenching of CDs has been rationalized on the basis of the increased nonradiative decay rate due to NSET from the CDs to the Ag NP surface. Various energy transfer related parameters have been estimated from the NSET theory and it has been observed that the NSET efficiency increases with the increase in the size of Ag NPs. This phenomenon has been explained by considering a larger spectral overlap and a shorter separation distance between the CDs and larger sized Ag NPs due to reduced electrostatic repulsion. Our present results reveal that the size of NPs plays an important role in the NSET process and this phenomenon can be easily utilized to tune the efficiency of energy transfer for various applications.

Luminescence turn-on/off sensing of biological iron by carbon dots in transferrin.

Iron is a key nutrient as well as a potential toxin for almost all living organisms. In mammalian cells, serum transferrin (Tf) is responsible for iron transport and its iron overload/deficiency causes various diseases. Therefore, closely regulated iron homeostasis is extremely essential for cellular metabolism. In the present article we report the pH-dependent luminescence turn-on/off sensing of bound Fe(3+) ions of serum Tf by carbon dots (CDs) with the help of photoluminescence (PL) spectroscopy, FTIR spectroscopy, dynamic light scattering (DLS), circular dichroism (CD) and PL imaging techniques. At physiological pH (7.4), the intrinsic luminescence of CDs gets quenched in the presence of Tf as a consequence of ground-state association, which is driven by favorable electrostatic interactions between negatively charged CDs (-25.45 ± 1.23 mV) and positively charged Fe(3+) ions of Tf. The estimated detection limit of Tf by CDs at physiological pH is found to be 1.82 µM (signal-to-noise ratio of 3), which is much lower than the in vivo plasma concentration of Tf (∼ 25-35 µM). Various thermodynamic parameters have been evaluated by using the van't Hoff equation. Importantly, the secondary structure of Tf remains unaltered upon association with CDs. However, at pH 3.5, no such luminescence quenching of CDs has been observed in the presence of Tf due to the lack of ground-state interactions between positively charged (+17.63 ± 0.84 mV) CDs and Tf. Furthermore, the results from UV-Vis and far-UV CD measurements revealed a significant conformational change of Tf at pH 3.5 relative to pH 7.4, which triggers the subsequent release of bound iron from Tf. PL microscopy of individual CD revealed significant luminescence quenching at the single particle level, which further supports the non-emissive ground-state complexation at pH 7.4. Our present results show that these chemically synthesized water-dispersed CDs have the ability to selectively sense the bound iron from released iron of Tf without any conformational perturbation and hence they can be used as potential biological iron sensors as well as luminescent markers for the detection of iron deficiency/overload in biological macromolecules.

Size-dependent penetration of carbon dots inside the ferritin nanocages: evidence for the quantum confinement effect in carbon dots.

The origin of the excitation wavelength (λex)-dependent photoluminescence (PL) of carbon dots (CDs) is poorly understood and still remains obscured. This phenomenon is often explained on the basis of surface trap/defect states, while the effect of quantum confinement is highly neglected in the literature. Here, we have shown that the λex-dependent PL of CDs is mainly due to the inhomogeneous size distribution. We have demonstrated the λex-dependent PL quenching of CDs inside the ferritin nanocages through selective optical excitation of differently sized CDs. It has been observed that Fe(3+) ions of ferritin effectively quench the PL of CDs due to static electron transfer, which is driven by favorable electrostatic interactions. However, control experiment with aqueous Fe(3+) ions in bulk medium revealed λex-independent PL quenching of CDs. The λex-dependent PL quenching of CDs by Fe(3+) ions of ferritin has been rationalized on the basis of a different extent of accessibility of Fe(3+) ions by differently sized CDs through the funnel-shaped ferritin channels. PL microscopy of individual CDs has been performed to get further information about their inherent PL properties at single dot resolution. Our results have shown that these hydrophilic CDs can be used as potential iron sensors in biological macromolecules.

Management of Type 2 diabetes in Ramadan: Low-ratio premix insulin working group practical advice.

The challenge of insulin use during Ramadan could be minimized, if people with diabetes are metabolically stable and are provided with structured education for at least 2-3 months pre-Ramadan. Although, American diabetes association (ADA) recommendations 2010 and South Asian Consensus Guideline 2012 deal with management of diabetes in Ramadan and changes in insulin dosage, no specific guidance on widely prescribed low-ratio premix insulin is currently available. Hence, the working group for insulin therapy in Ramadan, after collective analysis, evaluation, and opinion from clinical practice, have formulated a practical advice to empower physicians with pre-Ramadan preparation, dose adjustment, and treatment algorithm for self-titration of low-ratio premix insulin.

Concentration-dependent reversible self-oligomerization of serum albumins through intermolecular ß-sheet formation.

Proteins inside a cell remain in highly crowded environments, and this often affects their structure and activity. However, most of the earlier studies involving serum albumins were performed under dilute conditions, which lack biological relevance. The effect of protein-protein interactions on the structure and properties of serum albumins at physiological conditions have not yet been explored. Here, we report for the first time the effect of protein-protein and protein-crowder interactions on the structure and stability of two homologous serum albumins, namely, human serum albumin (HSA) and bovine serum albumin (BSA), at physiological conditions by using spectroscopic techniques and scanning electron microscopy (SEM). Concentration-dependent self-oligomerization and subsequent structural alteration of serum albumins have been explored by means of fluorescence and circular dichroism spectroscopy at pH 7.4. The excitation wavelength (λex) dependence of the intrinsic fluorescence and the corresponding excitation spectra at each emission wavelength indicate the presence of various ground state oligomers of serum albumins in the concentration range 10-150 µM. Circular dichroism and thioflavin T binding assay revealed formation of intermolecular ß-sheet rich interfaces at high protein concentration. Excellent correlations have been observed between ß-sheet content of both the albumins and fluorescence enhancement of ThT with protein concentrations. SEM images at a concentration of 150 µM revealed large dispersed self-oligomeric states with sizes vary from 330 to 924 nm and 260 to 520 nm for BSA and HSA, respectively. The self-oligomerization of serum albumins is found to be a reversible process; upon dilution, these oligomers dissociate into a native monomeric state. It has also been observed that synthetic macromolecular crowder polyethylene glycol (PEG 200) stabilizes the self-associated state of both the albumins which is contrary to expectations that the macromolecular crowding favors compact native state of proteins.

Microscopic evidence of "necklace and bead"-like morphology of polymer-surfactant complexes: a comparative study on poly(vinylpyrrolidone)-sodium dodecyl sulfate and poly(diallyldimethylammonium chloride)-sodium dodecyl sulfate systems.

Here, we report the microscopic evidence of "necklace and bead"-like morphology, which has long been the most widely accepted model for polymer-surfactant complexes. The lack of microscopic evidence of the initial complexation between surfactant and polymer has resulted in many contradictory reports in the literature. In this paper, we visualized these initial complexes formed between negatively charged surfactant sodium dodecyl sulfate (SDS) with neutral poly(vinylpyrrolidone) (PVP) and cationic poly(diallyldimethylammonium chloride) (PDADMAC) polymer through photoluminescence (PL) microscopy and atomic force microscopy (AFM) using silicon quantum dot (Si QD) as an external PL marker. It is observed that, for the PVP-SDS system, SDS molecules bind at the hydrophobic sites on the random-coiled PVP chain through their hydrocarbon tails, while for the PDADMAC-SDS system, SDS head groups are associated with the positively charged nitrogen centers of the polymer, where the polymer chain wraps around the surfactant head groups.