On the nature of initial solvation in bulk polar liquids: Gaussian or exponential?

Measurement of time evolution of fluorescence of a probe solute has been a quintessential technique to quantify how dipolar solvent molecules dynamically minimize the free energy of an electronically excited probe. During such solvation dynamics in bulk liquids, a substantial part of relaxation was shown to complete within sub-100 fs from time-gated fluorescence measurements, as also predicted by molecular dynamics simulation studies. However, equivalent quantification of solvation timescales by femtosecond pump-probe and broadband fluorescence measurements revealed an exponential nature of this initial relaxation having quite different timescales. Here, we set out to unveil the reason behind these puzzling contradictions. We introduce a method for estimating probe wavelength-dependent instrument response and demonstrate that the observation of the Gaussian vs exponential nature of initial relaxation is indeed dependent on the method of data analysis. These findings call for further experimental investigation and parallel development of theoretical models to elucidate the molecular-level mechanism accounting for different types of early time solvation.

Elucidating photocycle in large Stokes shift red fluorescent proteins: Focus on mKeima.

Large Stokes shift red fluorescent proteins (LSS-RFPs) are genetically encoded and exhibit a significant difference of a few hundreds of nanometers between their excitation and emission peak maxima (i.e., the Stokes shift). These LSS-RFPs (absorbing blue light and emitting red light) feature a unique photocycle responsible for their significant Stokes shift. The photocycle associated with this LSS characteristic in certain RFPs is quite perplexing, hinting at the complex nature of excited-state photophysics. This article provides a brief review on the fundamental mechanisms governing the photocycle of various LSS-RFPs, followed by a discussion on experimental results on mKeima emphasizing its relaxation pathways which garnered attention due to its >200 nm Stokes shift. Corroborating steady-state spectroscopy with computational studies, four different forms of chromophore of mKeima contributing to the cis-trans conformers of the neutral and anionic forms were identified in a recent study. Furthering these findings, in this account a detailed discussion on the photocycle of mKeima, which encompasses sequential excited-state isomerization, proton transfer, and subsequent structural reorganization involving three isomers, leading to an intriguing temperature and pH-dependent dual fluorescence, is explored using broadband femtosecond transient absorption spectroscopy.

Separating Vibrational Coherences in Ground/Excited Electronic States of Solvent/Solute Following Non-Resonant/Resonant Impulsive Excitation.

In a quest to track down the origin of coherent vibrational motions observed in femtosecond pump-probe transients, whether they arise from ground/excited electronic state of solute or are contributed by the solvent, we demonstrate a method for extricating vibrations under resonant and non-resonant impulsive excitations using a diatomic solute in condensed phase (iodine in carbon tetrachloride) with aid of spectral dispersion of the chirped broadband probe. Most importantly, we show how a sum over intensities for a select region of detection wavelengths and Fourier transform of data over select temporal window untwine contributions from vibrational modes of different origins. Thus, in a single pump-probe experiment, vibrational features specific to solute as well as solvent are disentangled that are otherwise spectrally overlapping and are non-separable in conventional (spontaneous/stimulated) Raman spectroscopy employing narrowband excitation. We envision wide-ranging applications of this method to unveil vibrational features in complex molecular systems.

Unveiling the Role of Hidden Isomers in Large Stokes Shift in mKeima: Harnessing pH-Sensitive Dual-Emission in Bioimaging.

Elucidating the origin of large Stokes shift (LSS) in certain fluorescent proteins absorbing in blue/blue-green and emitting in red/far-red has been quite illusive. Using a combination of spectroscopic measurements, corroborated by theoretical calculations, the presence of four distinct forms of the chromophore of the red fluorescent protein mKeima is confirmed, two of which are found to be emissive: a feeble bluish-green fluorescence (∼520 nm), which is enhanced appreciably in a low pH or deuterated medium but significantly at cryogenic temperatures, and a strong emission in red (∼615 nm). Using femtosecond transient absorption spectroscopy, the trans-protonated form is found to isomerize within hundreds of femtoseconds to the cis-protonated form, which further yields the cis-deprotonated form within picoseconds followed by structural reorganization of the local environment of the chromophore. Thus, the mechanism of LSS is substantiated to proceed via stepwise excited-state isomerization followed by proton transfer involving three isomers, leaving the fourth one (trans-deprotonated) as a bystander. The exquisite pH sensitivity of the dual emission is further exploited in fluorescence microscopy.

Electron-Phonon Coupling Mediated Self-Trapped-Exciton Emission and Internal Quantum Confinement in Highly Luminescent Zero-Dimensional (Guanidinium)6Mn3X12 (X = Cl and Br).

We report a large Stokes shift and broad emission band in a Mn-based organic-inorganic hybrid halide, (Guanidinium)6Mn3Br12 [GuMBr], consisting of trimeric units of distorted MnBr6 octahedra representing a zero-dimensional compound with a liquid like crystalline lattice. Analysis of the photoluminescence (PL) line width and Raman spectra reveals the effects of electron-phonon coupling, suggestive of the formation of Frenkel-like bound excitons. These bound excitons, regarded as the self-trapped excitons (STEs), account for the large Stokes shift and broad emission band. The excited-state dynamics was studied using femtosecond transient absorption spectroscopy, which confirms the STE emission. Further, this compound is highly emissive with a PL quantum yield of ∼50%. With chloride ion incorporation, we observe enhancement of the emissive properties and attribute it to the effects of intrinsic quantum confinement. Localized electronic states in flat bands lining the gap and their strong coupling with phonons are confirmed with first-principles calculations.

A Revisit on Impulsive Stimulated Raman Spectroscopy: Importance of Spectral Dispersion of Chirped Broadband Probe.

The usefulness of a chirped broadband probe and spectral dispersion to obtain Raman spectra under nonresonant/resonant impulsive excitation is revisited. A general methodology is presented that inherently takes care of phasing the time-domain low-frequency oscillations without probe pulse compression and retrieves the absolute phase of the oscillations. As test beds, neat solvents (CCl4, CHCl3, and CH2Cl2) are used. Observation of periodic intensity modulation along detection wavelengths for particular modes is explained using a simple electric field interaction picture. This method is extended to diatomic molecule (iodine) and polyatomic molecules (Nile blue and methylene blue) to assign vibrational frequencies in ground/excited electronic state that are supported by density functional theory calculations. A comparison between frequency-domain and time-domain counterparts, i.e., stimulated Raman scattering and impulsive stimulated Raman scattering using degenerate pump-probe pairs is presented, and most importantly, it is shown how impulsive stimulated Raman scattering using chirped broadband probe retains unique advantages offered by both.

Posology of insulins: A review of standard textbooks and product inserts.

OBJECTIVES: The study is aimed to assess whether the information contained in standard pharmacology, endocrinology, and diabetology textbooks regarding timings of administration, frequency and dose of various insulins is adequate and also to see whether the information contained in these texts is concordant with product inserts. MATERIALS AND METHODS: Four standard textbooks of pharmacology, two of diabetology and three of endocrinology were assessed for the published information regarding dose, timing, and frequency of insulin administration. The product inserts of commonly available insulins in India were also studied for the same. RESULTS: Various omissions and disparities could be seen in the coverage of insulins in standard textbooks. Posology information about premixed insulins and basal insulins have been omitted by the majority of the textbooks. Details about dose, frequency and timings of ultra-short acting insulins have also not been covered by all textbooks. Some discrepancies regarding prescribing information was also noted in product inserts, especially in case of newer insulins. CONCLUSIONS: Thus, this article stresses upon the need of a uniform source of information for providing adequate and standardized knowledge regarding timing, frequency, and dose of insulins.

Effect of diabetic education on the knowledge, attitude and practices of diabetic patients towards prevention of hypoglycemia.

AIMS: To assess the role of diabetic education in increasing awareness about hypoglycemia and decreasing hypoglycemic symptoms in diabetics. MATERIALS AND METHODS: This is a longitudinal study involving the use of a structured questionnaire for obtaining baseline information related to knowledge, attitude and practices (KAP) of diabetic patients regarding hypoglycemia. Then the patients were given diabetic education by the treating doctor regarding hypoglycemia, its symptoms and prevention; the effect of which was assessed by repeating the same questionnaire after a month. The occurrence of hypoglycemic symptoms was also compared before and after diabetic education. RESULTS: There is a significant improvement in all parameters like KAP with diabetic education. The hypoglycemic episodes also decrease significantly. CONCLUSIONS: Proper diabetic education is seen to improve the knowledge and attitude of the diabetic patients toward hypoglycemia. This leads to improved practices of such patients and decrease hypoglycemic episodes in them.

Bibliometric analysis of Indian Journal of Endocrinology and Metabolism.

BACKGROUND: Bibliometric analysis of the journal is a method to assess the research impact or research influence of that journal. This information can also be used to evaluate the influence/performance of a researcher and to provide a comparison between researchers. This work was aimed at performing bibliometric analysis of Indian Journal of Endocrinology and Metabolism (IJEM). MATERIALS AND METHODS: The publications of year 2011-12 of IJEM were analyzed. Total number of articles published, type of articles, their authorship, and the coverage of various subspecialties was studied. The publications were also classified as Indian or foreign, from endocrine or nonendocrine departments and from academic or nonacademic institutions according to the institution of first author. RESULTS AND CONCLUSIONS: A total of 10 main issues and 7 supplementary issues were published in IJEM in year 2011 and 2012. These included a total of 605 publications, which depict a dramatic increase in the number of publications in last 2 years as compared to the previous years. Taking collectively, review articles were published in majority. Maximum number of articles was dealing with pancreas and metabolic disorders followed by thyroid. Other endocrine organs were given almost similar importance. Publications were largely originating from endocrine departments and from academic institutions. Although maximum number of articles were from India, but the publications from other countries are also on an increase. Thus, the widespread coverage of this journal suggests that IJEM has begun to represent global face of Indian endocrinology.

Emerging therapies for the treatment of osteoporosis.

Osteoporosis is a chronic disease of the osseous system characterized by decreased bone strength and increased fracture risk. It is due to an imbalance in the dynamic ongoing processes of bone formation and bone resorption. Currently available osteoporosis therapies like bisphosphonates, selective estrogen receptor modulators (SERMs), and denosumab are anti-resorptive agents. Parathyroid hormone analogs like teriparatide are the only anabolic agents currently approved for osteoporosis treatment. The side-effects and limited efficacy of the presently available therapies has encouraged extensive research into the pathophysiology of the disease and newer drug targets for its treatment. The novel anti-resorptive agents being developed are newer SERMs, osteoprotegerin, c-src (cellular-sarcoma) kinase inhibitors, αVß3 integrin antagonists, cathepsin K inhibitors, chloride channel inhibitors, and nitrates. Upcoming anabolic agents include calcilytics, antibodies against sclerostin and Dickkopf-1, statins, matrix extracellular phosphoglycoprotein fragments activin inhibitiors, and endo-cannabinoid agonists. Many of these new drugs are still in development. This article provides an insight into the emerging drugs for the treatment of osteoporosis.

Comparison of fasting blood sugar and serum lipid profile changes after treatment with atypical antipsychotics olanzapine and risperidone.

INTRODUCTION: This study aimed to compare the effects of the two most commonly prescribed atypical antipsychotics, olanzapine and risperidone, on fasting blood sugar and serum lipid profile of the recipients. METHODS: A randomised, comparative, open clinical study was conducted on 60 schizophrenic patients. The patients were divided into two groups, one receiving olanzapine and the other receiving risperidone. The patients were assessed for changes in fasting blood sugar and serum lipid profile (triglycerides [TG], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very-low-density lipoprotein [VLDL] and total cholesterol) eight weeks after starting treatment. The number of patients positive for fasting blood sugar and lipid profile criteria of metabolic syndrome was calculated by applying the modified National Cholesterol Education Programme Adult Treatment Panel III guidelines (NCEP ATP III) criteria at eight weeks. RESULTS: Patients treated with olanzapine showed a highly significant increase in the observed parameters, whereas those treated with risperidone showed a significant increase in fasting blood sugar, HDL and LDL levels, and a highly significant increase in other parameters. Intergroup comparison was insignificant except for TG, VLDL and total cholesterol levels. More men as compared to women fulfilled the NCEP ATP III criteria for metabolic syndrome in both groups. CONCLUSION: Olanzapine has a higher propensity to cause derangement of some parameters of lipid profile than risperidone. These parameters include TG, VLDL and total cholesterol levels.