Patterns in behavioural sleep variables and social jetlag in elderly people of Western Odisha.

In humans, sleep is an essential physiological process for life and survival. The main objective of the current study is to determine the behavioural sleep patterns and social jetlag in elderly adults. The second objective is to define the relationship among subjective sleep quality, mid-sleep timings, social jetlag, and sunlight exposure. We recruited 945 female and 1047 male participants aged ≥ 60 years from 65 rural villages in the Sambalpur district of Odisha, India. The Munich Chrono Type Questionnaire (MCTQ) is a self-reported questionnaire that measures a person's behavioral sleep variables, including social jetlag and chronotype, whereas the Pittsburgh Sleep Quality Index (PSQI) measures the subjective sleep quality of an individual. We employed MCTQ and PSQI to obtain behavioral sleep variables and subjective sleep quality in the recruited subjects. The behavioral sleep variables were compared using a paired t-test on both work and work-free days. In addition, the behavioral sleep variables as a function of gender were compared using an independent Student's t-test. In the current study, most of the elderly individuals reported both midpoint of sleep on workdays (MSW) and midpoint of sleep on work-free days (MSF) between 00:01-03:00. The averages of mid-sleep timings between workdays and work-free days were not statistically significant. Data on MSFsc (midpoint of sleep on work-free days sleep corrected) indicated that most elderly adults (99.6%) are morning type; they go to bed early and wake up early. The elderly participants from the rural population of Sambalpur district in western Odisha had the least social jetlag and exhibited good subjective sleep quality. It would be worthwhile to find out the determinants of these positive features apropos social jetlag and behavioural sleep patterns.

Cerebral visual impairment in children: Multicentric study determining the causes, associated neurological and ocular findings, and risk factors for severe vision impairment.

Purpose: To evaluate the causes, associated neurological and ocular findings in children with cerebral visual impairment (CVI), and to identify risk factors for severe vision impairment. Methods: A multicenter, retrospective, cross-sectional analysis was carried out from January 2017 to December 2019 on patients less than 16 years of age with a diagnosis of CVI. Results: A total of 405 patients were included of which 61.2% were male and 38.8% were female. The median age at presentation was 4 years (range 3 months to 16 years). Antenatal risk factors were present in 14% of the cases. The most common cause of CVI was hypoxic-ischemic encephalopathy (35.1%), followed by seizure associated with brain damage (31.3%). The most common neurological finding was seizure (50.4%), followed by cerebral palsy (13.6%). Associated ophthalmological findings were significant refractive error (63.2%), esotropia (22.2%), exotropia, (38%), nystagmus (33.3%), and optic nerve atrophy (25.9%). Severe visual impairment (<20/200) was associated with optic atrophy (odds ratio: 2.9, 95% confidence interval: 1.4-6.0; P = 0.003) and seizure disorder (odds ratio: 1.9, 95% confidence interval: 1.2-3.3; P = 0.012). Conclusion: The various ophthalmic, neurological manifestations and etiologies could guide the multidisciplinary team treating the child with CVI in understanding the visual impairment that affects the neuro development of the child and in planning rehabilitation strategies.

A Fluorescence Study of the Interaction of Anticancer Drug Molecule Doxorubicin Hydrochloride in Pluronic P123 and F127 Micelles.

Drug delivery systems for the sustained and target delivery of doxorubicin to tumor cells are a topic of interest due to the efficacy of the doxorubicin in cancer treatment. The use of polymers such as Pluronic is being studied widely for the formulation of doxorubicin hydrochloride. However, the basic understanding of the physicochemical properties of pluronic micelles in presence of doxorubicin hydrochloride is a very essential topic of study. Doxorubicin hydrochloride is fluorescent; this helped us to study its sensitivity towards the Pluronic microenvironment using the fluorescence technique. In this work, the interaction and place of location of doxorubicin hydrochloride in Pluronic F127 and P123 micelles has been studied extensively using steady-state fluorescence intensity, dynamic fluorescence lifetime, quenching studies, dynamic light scattering, and zeta potential measurements, at different Pluronic concentrations. Using a fluorescence quenching experiment, doxorubicin hydrochloride was found to reside near the hydrophilic PEO corona region of the Pluronic micelles. For both the Pluronic, in the concentration range of study, the micellar size was found to be below 30 nm; this may have a greater advantage for various applications.

Excited state proton transfer based fluorescent molecular probes and their application in studying lipid bilayer membranes.

Molecules with ionizable protons, with different proton transfer efficiencies in the excited and ground states, show excited state prototropism (ESPT). In suitable proton donating/accepting environments, ESPT of a molecule can result in the observation of emissions from different prototropic species, each characterized by different emission spectra and different emission lifetimes. In condensed media, the immediate environment around the ESPT molecule can significantly influence the emission spectral parameters of different prototropic species. This forms the basis of ESPT based fluorescence sensing. The concept of ESPT has been widely used for probing dynamical and structural information of micro-heterogeneous media like micelles, polymers, lipid bilayer membranes, etc. ESPT molecules like naphthol and intra-molecular ESPT (ESIPT) molecules like hydroxyflavones etc., are said to be good multi-state fluorescent molecular probes if (i) the partitioning of these molecules to a micro-heterogeneous organized medium is more efficient, and (ii) the molecules possess distinct excitation and emission wavelengths corresponding to their different prototropic forms. The fluorescence of different prototropic forms shows a sensitive response towards the change in the local environment around the micro-heterogeneous organized medium concerning the physical properties, local structure, and dynamics. This review mainly comprises the work carried out on ESPT fluorescence molecular probing of biomimetic liposomes/lipid bilayer membranes from 1990 onwards.

Fluorescence of N-acylated dansylamide with a long hydrophobic tail: sensitive response to premicellar aggregation of sodium deoxycholate.

The present work describes the synthesis and photophysical studies of two fluorescent dansylamide derivatives, in which the amine group is acylated by a long hydrophobic chain (a part of a biologically relevant palmitic acid) and by a short hydrophobic tail (a part of acetic acid). The long chain tethered dansyl analogue is successfully utilized in estimating critical micellar concentration (CMC) of bile salts (NaDC, NaC) as well as anionic and cationic surfactants (SDS, CTAB) with the help of enhanced fluorescence intensity facilitated by better solubilization of the molecule in microheterogeneous media. The long chain tethered dansylamide derivative shows significant fluorescence solvatochromism with a red shift (ca. 4000 cm(-1)) from hexane to water. In contrast, the solvatochromism exhibited by the parent/short acyl chain analogue is much less (ca. 2230 cm(-1) from hexane to water) and the fluorescence is not sensitive to micellization. Interestingly, the long chain tethered fluorescent probe shows high sensitivity towards premicellar aggregation of sodium deoxycholate (NaDC) bile salt, through a clear blue shift of emission maxima and concomitant enhancement of fluorescent intensity. Such an observation of fluorescence sensing of premicellar aggregation is unusual.

Photophysical behavior of a new cholesterol attached coumarin derivative and fluorescence spectroscopic studies on its interaction with bile salt systems and lipid bilayer membranes.

A new fluorescent-cholesterol (Cum-Chl) molecule has been synthesized by attaching 3-acetyl-7-(diethylamino)-2H-chromen-2-one (Cum) to cholesterol via cholesterol bound ß-keto ester. The ß-keto ester was synthesized from the corresponding nitrile by applying the Blaise reaction. The molecule forms H-aggregates in solutions. The efficiency of aggregation is high in water. The H-aggregates are non-fluorescent in non-aqueous solvents but fluorescent in water. Aqueous bile salt media suppress the formation of H-aggregates, this effect being more pronounced for sodium deoxycholate (NaDC) which is more hydrophobic. With increasing bile salt concentration, the enhancement of monomeric fluorescence intensity of Cum-Chl generally follows the progressive miceller aggregation of bile salts. Incorporation of Cum-Chl into the dimyristoylphosphatidylcholine (DMPC) lipid bilayer membrane results in a significant enhancement of monomeric fluorescence intensity. The variation of fluorescence intensity is also sensitive to the thermotropic phase transition of the bilayer. It is seen that in such aqueous micro- and nanoscale organized media like bile salts and lipid bilayer membranes the monomer-to-aggregate fluorescence intensity ratio reflects the state of organization of the medium.

Study of aqueous phase aggregation of FTY720 (fingolimod hydrochloride) and its effect on DMPC liposomes using fluorescent molecular probes.

This work focuses on the study of aqueous phase aggregation of the recently FDA approved oral drug molecule FTY720 (fingolimod hydrochloride) and its effect on dimyristoylphosphatidylcholine (DMPC) liposomes using different fluorescent molecular probes and fluorescence parameters. The variation of the steady state fluorescence intensity of 8-anilino-1-naphthalene sulfonic acid (ANS) with FTY720 in water shows an efficient micellar aggregation with the critical micellar concentration (CMC) at ~75 µM. The aggregation number calculation from steady state fluorescence quenching of pyrene shows the formation of small micellar aggregates in aqueous solution having an aggregation number of 42 ± 3 with the free energy of micellization ~-23 kJ mol(-1). Fluorescence intensity and lifetime decay analysis of the molecular probe 1-naphthol indicate that the interaction of FTY720 with the DMPC lipid bilayer membrane prevents partitioning of small molecules such as 1-naphthol to the membrane in both solid gel (SG) and liquid crystalline (LC) phases. Temperature dependent fluorescence intensity studies of 1-naphthol and fluorescence anisotropy measurements of 1,6-diphenyl-1,3,5-hexatriene (DPH) have shown that above the CMC of FTY720, the SG to LC main phase transition temperature (T(M)) of the lipid bilayer membrane decreases from 23 °C to 21 °C in the aqueous medium.

Photophysical behavior of 8-anilino-1-naphthalenesulfonate in vesicles of pulmonary surfactant dipalmitoylphosphatidylcholine (DPPC) and its sensitivity toward the bile salt-vesicle interaction.

The photophysical behavior of 8-anilino-1-naphthalenesulphonate (ANS) in vesicles of dipalmitoylphosphatidylcholine (DPPC), a pulmonary surfactant, has been carried out in a detailed manner. ANS shows notable variations in fluorescence intensity, lifetime, and anisotropy parameters as it gets into the vesicle. It was found that ANS partitions well into the DPPC bilayer membrane with an estimated partition coefficient of ~2.0 × 10(5). Among the various fluorescence parameters of ANS, fluorescence anisotropy was found to be most responsive to the temperature induced phase change of the bilayer membrane. These interesting fluorescence parameters of ANS were then used to study the hydration of lipid bilayer membrane by submicellar concentration of bile salts. From the steady-state fluorescence intensity and dynamic fluorescence lifetime analyses it is clear that ANS is able to probe the submicellar concentration (≤1 mM) of bile salt induced hydration of lipid bilayer membrane that accompanies expulsion of ANS from the bilayer to the aqueous bulk phase. Lower-temperature shift in the phase transition of DPPC bilayer indicates that fluorescence anisotropy of ANS is sensitive enough to the bile salt induced perturbation in the packed acyl chains of DPPC bilayer and modification in the membrane fluidity. In presence of sodium deoxycholate (NaDC) and sodium cholate (NaC) in DPPC vesicles, ANS experiences restriction in rotational mobility which is evident from the variation in steady-state fluorescence anisotropy and fluorescence anisotropy decay parameters.

Deciphering the photophysical role of conjugated diyne in butadiynyl fluorophores: synthesis, photophysical and theoretical study.

The present work focuses on the current interest in diyne bridged chromophores necessitating a clearer understanding of the photophysics of such molecules. The significance of the diyne moiety in the photophysics has been investigated by synthesizing simple substituted diphenyl butadiynyl derivatives following a quick and efficient microwave assisted Eglinton coupling of terminal alkynes. Emission of the fluorophores is observed from the usual locally excited (LE) state and intramolecular charge transfer (ICT) state. Separation of pure ICT emission from pure LE emission has been carried out by Gaussian/Lorentzian curve fitting. The vibronic coupling in the local transitions appears to be confined to the normal mode involving the C-C triple bond stretching of the diyne moiety. This implies that the LE transition involves the diyne moiety, a conclusion supported by quantum chemical calculations. The resolved ICT emission follows double linear dependence on ET(30) solvent polarity scale. The important role of the diyne moiety in the photophysics of this class of molecules is clearly discernible in this study.

Effect of submicellar concentrations of conjugated and unconjugated bile salts on the lipid bilayer membrane.

The interaction of submicellar concentrations of various physiologically important unconjugated [sodium deoxycholate (NaDC), sodium cholate (NaC)] and conjugated [sodium glycodeoxycholate (NaGDC), sodium glycocholate (NaGC), sodium taurodeoxycholate (NaTDC), sodium taurocholate (NaTC)] bile salts with dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) small unilamellar vesicles in solid gel (SG) and liquid crystalline (LC) phases was investigated using the excited-state prototropism of 1-naphthol. Steady-state and time-resolved fluorescence of the two excited-state prototropic forms of 1-naphthol indicate that submicellar bile salt concentration induces hydration of the lipid bilayer membrane into the core region. This hydration effect is a general phenomenon of the bile salts studied. The bilayer hydration efficiency of the bile salt follows the order NaDC > NaC > NaGDC > NaTDC > NaGC > NaTC for both DPPC and DMPC vesicles in their SG and LC phases.

Photophysical behavior of fisetin in dimyristoylphosphatidylcholine liposome membrane.

A detailed photophysical study of the plant flavonoid fisetin in a dimyristoylphosphatidylcholine (DMPC) bilayer membrane has been carried out. Fisetin is found to partition well into the membrane (K(p) = (4.6 ± 0.5) × 10(5) in solid gel phase and (5.1 ± 0.5) × 10(5) in liquid crystalline phase). A fluorescence quenching study using cetylpyridinium chloride (CPC) as the quencher suggests that fisetin molecules are generally present near the head group region of the lipid bilayer membrane. The temperature dependence of the fluorescence lifetime indicates a local heterogeneity in the distribution of fisetin within the bilayer membrane. The phototautomer form of fisetin, which is the primary emitting species from the lipid membrane, has a large Stoke's shift (175 nm) and fluoresces with an intense green fluorescence, which can make the molecule a good dye for marker and bioimaging applications. Membrane-bound fisetin shows sensitive variations of fluorescence intensity, lifetime, and anisotropy parameters in cholesterol-containing DMPC membranes, in mixed phospholipids, and as a function of temperature. This suggests that fisetin can be an efficient fluorescent molecular probe for sensing lipid bilayer membrane related changes. The location of fisetin in the membrane and the observed cholesterol-induced expulsion of fisetin may possibly have implications in the antioxidant activity of fisetin.

1-Naphthol as a sensitive fluorescent molecular probe for monitoring the interaction of submicellar concentration of bile salt with a bilayer membrane of DPPC, a lung surfactant.

In this study, 1-naphthol has been used as a sensitive ESPT fluorescent molecular probe to investigate the interaction of submicellar concentrations of two physiologically important bile salts, sodium deoxycholate and sodium cholate, with dipalmitoylphosphatidylcholine small unilamellar vesicles in solid gel and liquid crystalline phases. Steady-state and time-resolved fluorescence of the two excited state prototropic forms of 1-naphthol indicate that the incorporation of monomeric bile salt molecules in the lipid bilayer membrane induces appreciable wetting of the bilayer up to the hydrocarbon core region, even at very low (≤1 mM) concentrations of the bile salts.

Photophysical behaviour of ground state anion and phototautomer of 3-hydroxyflavone in liposome membrane.

A detailed account of the photophysical behaviour of the phototautomer (PT) and the ground state anion (A-) of 3-hydroxyflavone in liposome membrane at various membrane conditions is presented. A quenching study with a hydrophilic quencher Ag+ suggests that the phototautomeric emission generates from the fraction of 3HF that is located at the inner hydrophobic core, whereas the ground state anionic emission is from the fraction that resides near the water-accessible surface site. However, the biexponential nature of fluorescence decays of both the forms indicates that there is local heterogeneity in the distribution. Temperature dependence studies and experiments in the presence of ethanol reveal that, as the membrane becomes more fluid, redistribution of 3HF takes place between the two sites leading to increase in A- population. The temperature dependence of the fluorescence anisotropy change of PT shows good correlation with the phase change and shows a sharp drop at the transition temperature, whereas the corresponding change in the case of A- is gradual.