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Background: CSOM is associated with functional damage to the ear which can present as SNHL; however published literature shows mixed associations. Study design and setting: Cross-sectional observational study at Jinnah Postgraduate Medical Center, Karachi, Pakistan. Methodology: The study sampling technique was non-probability consecutive sampling technique. Patients of either gender and between the ages of 10-50 years, diagnosed with CSOM within the last six months were included while patients with a previous history of SNHL, usage of ototoxic drugs, trauma to ear or those not willing to give consent for the study were excluded. SPSS v23.0 was used for data analysis and chi-square test was applied, keeping p-value of <0.05 as statistically significant. Results: From the total of 200 patients with mean age of patients 24.7 ± 8.42 years. The mean duration of CSOM was 6.56 ± 4.28 years. 145 (72.5 %) were male while 55 (27.5 %) female. SNHL was found to be positive in 36 (18 %) of patients while 165 (82 %) were negative for SNHL. With respect to duration to disease, SNHL was reported to be positive in 11 (10.9 %) of patients having duration of CSOM between 2-6 years while in 25 (25.3 %) of patients having CSOM for over 6 years. A significant difference of p-0.008 was observed in both the groups. Conclusion: According to the results of this study, SNHL is significantly associated with CSOM with higher frequencies observed in males and in patients with CSOM for longer durations. [ABSTRACT FROM AUTHOR]

Degradation scheme for the photolytic degradation of methylcobalamin (MC) in the presence of ascorbic acid (AH 2). [Display omitted] • Photodegradation of methylcobalamin in the presence of ascorbic acid (AH 2). • Application of linear and non-linear correction of irrelevant absorption. • First-order rate constant for the photodegradation of MC is determined. • Second-order rate constants for photochemical interaction of MC and AH 2. • Fluorescence characteristic of MC in the presence of AH 2 is determined. Photodegradation of drug substances leads to the formation of known and unknown degradation products. These unknown degradation products interfere and give erroneous results because of absorption on analytical wavelengths. This interference could be eliminated using the correction of irrelevant absorbancies. This study is based on the application of linear and non–linear correction of irrelevant absorption for the determination of methylcobalamin (MC) and hydroxocobalamin in the photolytic degradation assisted by ascorbic acid (AH 2). MC follows first–order degradation kinetics and the rate of degradation (k obs) ranges from 1.99–2.34 × 10−2, min−1 at pH 2.0–12.0. The second–order rate constants (k 2) for the photochemical interaction of MC and AH 2 are in the range of 17.9–60.3 × 10−2 M−1, min−1 (acidic region) and 10.3–24.6 × 10−2 M−1, min−1 (alkaline region). The k 2 –pH profile was found to be bell–shaped and the maximum rate of degradation in the presence of AH 2 is at pH 5.0 (60.3 × 10−2 M−1, min−1) due to the protonation of MC. However, in alkaline pH, the rate of photodegradation decreases due to the ionization form of AH 2 which is AH− species. [ABSTRACT FROM AUTHOR]

7,8‐Dimethoxy‐3‐methyl‐1,10‐ethylenealloxazinium chloride (1a) was found to be a superior photooxidation catalyst among substituted ethylene‐bridged flavinium salts (R=7,8‐diMeO, 7,8‐OCH2O‐, 7,8‐diMe, H, 7,8‐diCl, 7‐CF3 and 8‐CF3). Selection was carried out based on structure vs catalytic activity and properties relationship investigations. Flavinium salt 1a proved to be robust enough for practical applications in benzylic oxidations/oxygenations, which was demonstrated using a series of substrates with high oxidation potential, i. e. 1‐phenylethanol, ethylbenzene, diphenylmethane and diphenylmethanol derivatives substituted with electron‐withdrawing groups (Cl or CF3). The unique capabilities of 1a can be attributed to its high photostability and participation via a relatively long‐lived singlet excited state, which was confirmed using spectroscopic studies, electrochemical measurements and TD‐DFT calculations. This allows the maximum use of the oxidation power of 1a, which is given by its singlet excited state reduction potential of +2.4 V. 7,8‐Dichloro‐3‐methyl‐1,10‐ethylenealloxazinium chloride (1 h) can be used as an alternative photocatalyst for even more difficult substrates. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ascorbic acid (AH 2) photodegradation increases at pH 2.0–12.0 by riboflavin (RF). • Ionized species (AH-) of AH 2 are more prone to photodegradation. • RF acts as a photosensitizer for the photooxidation of AH 2. • A two-component spectrophotometric method can be used for the assay of AH 2 and RF in aqueous solutions. Ascorbic acid (AH 2) photoxidation sensitized by riboflavin (RF) has been studied between pH 2.0 and 12.0 in ambient air and anaerobic environment using UV and visible irradiation sources. The kinetics of AH 2 degradation in aqueous medium along with RF is found to be first-order for its photodegradation. AH 2 photolysis rate constants in aerobic and anaerobic conditions with RF (1.0–5.0 × 10-5 M) are 0.14–3.89 × 10-2 and 0.026–0.740 × 10-2 min−1, respectively. The rate constants (k 2) of second-order kinetics for AH 2 and RF photochemical interaction in aerobic and anaerobic conditions are in the range of 0.24–3.70 to 0.05–0.70 × 10-3 M−1 min−1, respectively, which manifests that increasing the RF concentration also increases the rate of photodegradation (photooxidation) of AH 2. The k 2 versus pH graph is bell-shaped which indicates that increasing the pH increases photolytic degradation rate of AH 2 with RF. Increasing the pH results in the increased ionization of AH 2 (ascorbyl anion, AH-) and redox potential which leads to the higher rates of photodegradation of AH 2. Two–component spectrophotometric (243 and 266 nm, AH 2 and RF, respectively) and high-performance liquid chromatography (HPLC) methods have been used to determine the concentration of AH 2 and RF in pure and degraded solutions. The results obtained from these two methods are compared using a student t-test which showed no noteworthy difference between them. [ABSTRACT FROM AUTHOR]

• Riboflavin conjugated silver nanoparticles (RF-AgNPs) have been prepared to improve the photostability of RF. • RF-AgNPs exhibit a typical plasmon resonance band at 422 nm. • FTIR spectrum shows an absorption band at 2920 cm−1 due to RF-Ag interaction. • The formation of RF–AgNPs involves a biphasic first–order reaction. • An increase in the pH range 8.0–10.5 affects the particle size of RF-AgNPs. Riboflavin conjugated silver nanoparticles (RF–AgNPs) have been synthesized by photoreduction of Ag+ ions and characterized by UV–visible, X-ray diffraction (XRD), FTIR spectroscopy, spectrofluorimetry, dynamic light scattering (DLS) and atomic force microscopy (AFM). The RF–AgNPs exhibit a typical surface plasmon resonance (SPR) peak at 422 nm due to the interaction of RF and AgNPs. FTIR studies indicate the appearance of an intense absorption peak at 2920 cm–1 due to the interaction of RF and Ag. AFM studies indicate that the RF–AgNPs are spherical and polydisperse in nature (57–73 nm), which nicely complement the hydrodynamic radii (57.9–72.2 nm) measured by DLS. None of the tested concentrations (1-250 µg mL−1) of RF–conjugated AgNPs show any adverse effect on normal mouse fibroblast and cancerous non-small lung carcinoma cell lines. At acidic pH (2.0–6.2) aggregation of RF–AgNPs occurs due to an increase in the ionic strength of the medium. The rates of formation of RF–AgNPs on UV and visible light irradiation have been determined in the pH range of 8.0–10.5 and at different concentrations of Ag+ ions. The photochemical formation of RF–AgNPs follows a biphasic first–order reaction probably due to the formation of AgNPs in the first phase (fast) and the adsorption of RF on AgNPs to yield RF–AgNPs in the second phase (slow). [Display omitted] [ABSTRACT FROM AUTHOR]

The effect of metal ion complexation on the photolysis of riboflavin (RF) using various metal ions (Ag + , Ni 2 + , Co 2 + , Fe 2 + , Ca 2 + , Cd 2 + , Cu 2 + , Mn 2 + , Pb 2 + , Mg 2 + , Zn 2 + , Fe 3 + ) has been studied. Ultraviolet and visible spectral and fluorimetric evidence has been obtained to confirm the formation of metal-RF complexes. The kinetics of photolysis of RF in metal-RF complexes at pH 7.0 has been evaluated. The apparent first-order rate constant ( k obs ) for the photolysis of RF and the formation of lumichrome (LC) and lumiflavin (LF) (0.001 M phosphate buffer) and LC, LF and cyclodehydroriboflavin (CDRF) (0.2–0.4 M phosphate buffer) have been determined. The values of k obs indicate that the rate of photolysis of RF is promoted by divalent and trivalent metal ions. The second-order rate constants ( k ʹ ) for the interaction of metal ions with RF are in the order: Zn 2 + > Mg 2 + > Pb 2 + > Mn 2 + > Cu 2 + > Cd 2 + > Fe 2 + > Ca 2 + > Fe 3 + > Co 2 + > Ni 2 + > Ag + . In phosphate buffer (0.2–0.4 M), an increase in the metal ion concentration leads to a decrease in the formation of LC compared to that of CDRF by different pathways. The photoproducts of RF have been identified and RF and the photoproducts have simultaneously been assayed by a multicomponent spectrometric method. The mode of photolysis of RF in metal-RF complexes has been discussed. [ABSTRACT FROM AUTHOR]

A study of the effect of ionic strength on the photodegradation reactions (photoreduction and photoaddition) of riboflavin (RF) in phosphate buffer (pH 7.0) has been carried out using a specific multicomponent spectrometric method. It has been found that the rates of photodegradation reactions of RF are dependent upon the ionic strength of the solutions at different buffer concentrations. The apparent first-order rate constants ( k obs ) for the photodegradation of riboflavin at ionic strengths of 0.1–0.5 (0.5 M phosphate) lie in the range of 7.35–30.32 × 10 − 3 min − 1 . Under these conditions, the rate constants for the formation of the major products, lumichrome (LC) by photoreduction pathway, and cyclodehydroriboflavin (CDRF) by photoaddition pathway, are in the range of 3.80–16.03 and 1.70–6.07 × 10 − 3 min − 1 , respectively. A linear relationship has been observed between log k obs and √ μ/1 + √ μ. A similar plot of log k/k o against √ μ yields a straight line with a value of ~+1 for Z A Z B showing the involvement of a charged species in the rate determining step. NaCl appears to promote the photodegradation reactions of RF probably by an excited state interaction. The implications of ionic strength on RF photodegradation by different pathways and flavin–protein interactions have been discussed. [ABSTRACT FROM AUTHOR]

We present a methodology to analyze the stationary states and stability of complex fluid flows by using hybrid, discrete, and/or continuum multi-scale simulations. Building on existing theories, our scheme extracts dynamical and equilibrium characteristics from carefully chosen time integrations of these multi-scale evolution equations. Two canonical problems are presented to demonstrate the ability and accuracy of the formalism. The first is an investigation of flow-induced transitions seen in homogeneous, hard- rod liquid crystal suspensions subjected to a linear shear flow. In the second problem, we study the phenomenon of draw resonance, a dynamical instability in an isothermal fiber-spinning process, by using a multi-scale hybrid simulation that incorporates both stochastic and continuum models. [ABSTRACT FROM AUTHOR]

Abstract: Kinetic theory models exhibit dynamics that depend on a few low-order moments of the underlying conformational distribution function. This dependence is exhibited in a compact spectrum of eigenvalues for the Jacobian matrix associated with the dynamical system. We take advantage of this spectrum of eigenvalues through Newton-GMRES iterations to enable dynamic viscoelastic simulators (time-steppers) to obtain stationary states and perform stability/bifurcation analysis. Results are presented for three example problems: (1) the equilibrium behavior of the Doi model with the Onsager excluded volume potential, (2) pressure-driven flow of non-interacting rigid dumbbells in a planar channel, and (3) pressure-driven flow of non-interacting rigid dumbbells through a planar channel with a linear array of equally spaced cylinders. [Copyright &y& Elsevier]

Keywords: Aerobic oxidation; Electron transfer; Photochemistry; Photoredox catalysis; Spectroscopy EN Aerobic oxidation Electron transfer Photochemistry Photoredox catalysis Spectroscopy 4283 4283 1 09/23/21 20210921 NES 210921 The B front cover picture b , prepared by Dr D. Prukala, illustrates ethylene-bridged 7,8-dimethoxyflavinium salt excited with blue light. Front Cover Picture: Robust Photocatalytic Method Using Ethylene-Bridged Flavinium Salts for the Aerobic Oxidation of Unactivated Benzylic Substrates (Adv. Aerobic oxidation, Electron transfer, Photochemistry, Photoredox catalysis, Spectroscopy. [Extracted from the article]

The photolysis of thiochrome (THC), an oxidation product of thiamine (vitamin B 1) (THE), used for its fluorimetric assay, has been studied in the pH range 7.0–12.0. THC undergoes photooxidation to oxodihydrothiochrome (ODTHC) which is oxidized to a non-fluorescent compound (OP1) on UV irradiation. The kinetics of the consecutive first-order reactions: THC → k 1 ODTHC → k 2 OP 1 , has been evaluated and the values of first-order rate constants, k 1 (0.58–4.20 × 10−5, s−1) and k 2 (0.05–2.03 × 10−5, s−1), at pH 7.0–12.0 have been determined. The rates of degradation of THC and ODTHC are enhanced with pH and the second-order rate constants k 1 ʹ and k 2 ʹ for the OH– ion-catalyzed reaction are in the range of 0.002–58.3 M−1 s−1. The quantum yields of the photolysis of THC and ODTHC in the pH range 7.0–12.0 have been determined. THC, ODTHC and OP1 have been identified by chromatographic, spectrometric and fluorimetric methods. THC and ODTHC have similar fluorescence characteristics and emit at 450 and 445 nm, respectively. THC, ODTHC and OP1 with distinct absorption maxima (370, 344 and 290 nm, respectively) have been determined by a newly developed and validated multicomponent spectrometric method during the photolysis reactions. The on-line formation of THC by the photooxidation of THE may lead to the degradation of THC and give erroneous results in the fluorimetric assay of THE. A scheme for the photolysis reactions of THC in aqueous solution is presented. Unlabelled Image • Photolysis of thiochrome (THC) by UV light has been studied in the pH range 7.0–12.0. • THC is photooxidized to oxodihydrothiochrome (ODTHC) in alkaline solution. • Photolysis of THC follows consecutive first-order kinetics to form oxidation products. • THC photolysis is pH dependent and is enhanced with pH in alkaline solution. • THC and photoproducts have been assayed by a multicomponent spectrometric method. [ABSTRACT FROM AUTHOR]

Graphical abstract Formylmethylflavin (FMF) on absorption of light is promoted to excited triplet state which on H abstraction forms a diradical intermediate. This is converted to a cyclic ketone that leads to the formation of carboxymethylflavin (CMF), lumichrome (LC), lumiflavin (LF), formic acid and acetic acid. FMF on alkali hydrolysis of isoalloxazine ring forms quinoxaline derivative, KA and DQ. Highlights • Photodegradation of formylmethylflavin (FMF) at pH 8.0–12.0 has been studied. • FMF degrades by side–chain cleavage to lumichrome (LC) and lumiflavin (LF). • It also degrades by isoalloxazine ring cleavage to form quinoxaline derivatives. • Kinetics of alkaline photodegradation reactions of FMF has been evaluated. • FMF and photoproducts have been assayed by a spectrofluorimetric method. Abstract The photodegradation of fromylmethylflavin (FMF), a major intermediate product in the photolysis of riboflavin, in the pH range 8.0–12.0 has been studied. FMF undergoes photodegradation by side–chain cleavage to give lumichrome (LC) and lumiflavin (LF) in alkaline solution. It is also degraded by the hydrolysis of isoalloxazine ring to form 1,2–dihydro–1–methyl–2–keto–3–quinoxaline carboxylic acid (KA) and 1,2,3,4–tetrahydro–1–methyl–2,3–dioxoquinoxaline (DQ) and is oxidized to carboxymethylflavin (CMF) in alkaline solution. The photodegradation of FMF follows simultaneous first–order kinetics to form the side–chain, ring cleavage and oxidation products. The apparent first–order rate constants (k obs) for these reactions have been determined and are in the range of 0.15 (pH 8.0) to 4.98 × 102 min–1 (pH 12.0). The rate constants for the formation of the photoproducts (LC, LF, CMF, KA, DQ) have also been determined. The formation of the photoproducts is enhanced with pH due to the sensitivity of flavin triplet to alkaline hydrolysis. FMF and photodegradation products have been determined by a multicomponent spectrofluorimetric method in degraded solutions. It involves the separation of LC and LF by chloroform extraction at pH 2 followed by the choloroform extraction of undegraded FMF at pH 6.5 and their assay at 478 (LC) and 530 nm (LF and FMF), respectively. The aqueous phase is used for the assay of CMF, KA and DQ at 530, 443 and 420 nm, respectively. The mode of photodegradation of FMF has been discussed. [ABSTRACT FROM AUTHOR]

Abstract A multicomponent spectrofluorimetric method has been developed for the simultaneous assay of formylmethylflavin (FMF), an intermediate product in the photolysis of riboflavin (vitamin B 2 ), and its side-chain hydrolytic products, lumichrome (LC) in acidic solution and LC and lumiflavin (LF) in the alkaline solution as well as its ring cleavage products, 1,2-dihydro-1-methyl-2-keto-3-quinoxaline carboxylic acid (KA) and 1,2,3,4-tetrahydro-1-methyl-2,3-dioxo-quinoxaline (DQ) in alkaline solution. The assay method also takes into account an oxidation product of FMF, i.e. carboxymethylflavin (CMF), in both acid and alkaline solutions. The method involves adjustment of the pH of hydrolysed solution to 2.0 to convert FMF to its protonated form, extraction of LC (acid solution) or LC and LF (alkaline solution) with chloroform and their simultaneous assay by fluorescence measurement at 478 and 530 nm, respectively. The aqueous phase is readjusted to pH 6.5, extracted with chloroform to remove undegraded FMF and used for the assay of CMF, KA and DQ at 530, 443 and 420 nm, respectively. The chloroform extract is used for the assay of FMF at 530 nm. The proposed method has been validated and applied to the study of the kinetics of a hydrolysis reaction of FMF at pH 11.0. The calibration curves for FMF and degradation products are linear in the range of 0.1–1.0 × 10−6 M. The limit of detection (LOD) and limit of quantification (LOQ) range from 2.54–5.75 × 10−8 M and 0.78–1.74 × 10−7 M, respectively, for these compounds. The mean recovery ranges from 99.3–102.1% with a RSD of 0.14–0.35%. Judging from the molar balance of FMF and the hydrolytic products, uniformity of analytical data during the reactions and linearity of kinetic plot, the method gives accurate results for the assay of FMF and all of its degradation products. It can be conveniently used for the assay of these compounds and for the kinetics and stability studies of FMF. Graphical Abstract A scheme for the spectrofluorimetric assay of formylmethylflavin and its alkaline hydrolysis products is presented. The method involves chloroform extraction at the initial stage and assay of its two side-chain cleavage products in chloroform extract and one of side-chain and two of isoalloxazine ring cleavage products in aqueous phase independently at their respective fluorescence maxima. Unlabelled Image Highlights • A fluorimetric method is developed to assay formylmethylflavin (FMF) and degradants. • The fluorescence characteristics of FMF and degradation products have been determined. • The method can simultaneously determine five components in a mixture. • The method has been validated according to ICH guideline. • It has been applied to study the kinetics of FMF hydrolysis in aqueous solution. [ABSTRACT FROM AUTHOR]

Flavins are a unique class of compounds that combine the features of singlet oxygen generators and redox-dependent fluorophores. From a broad family of flavin derivatives, deazaalloxazines are significantly underdeveloped from the point of view of photophysical properties. Herein, we report photophysics of 5-deazaalloxazine (1a) in water, acetonitrile, and some other solvents. In particular, triplet excited states of 1a in water and in acetonitrile were investigated using ultraviolet–visible (UV–Vis) transient absorption spectroscopy. The measured triplet lifetimes for 1a were all on the microsecond time scale (≈ 60 μs) in deoxygenated solutions. The quantum yield of S1 → T1 intersystem crossing for 1a in water was 0.43 based on T1 energy transfer from 1a to indicaxanthin (5) acting as acceptor and on comparative actinometric measurements using benzophenone (6). 1a was an efficient photosensitizer for singlet oxygen in aerated solutions, with quantum yields of singlet oxygen in methanol of about 0.76, compared to acetonitrile ~ 0.74, dichloromethane ~ 0.64 and 1,2-dichloroethane ~ 0.54. Significantly lower singlet oxygen quantum yields were obtained in water and deuterated water (ФΔ ~ 0.42 and 0.44, respectively). Human red blood cells (RBC) were used as a cell model to study the antioxidant capacity in vitro and cytotoxic activity of 1a. Fluorescence-lifetime imaging microscopy (FLIM) data were analyzed by fluorescence lifetime parameters and distribution for different parts of the emission spectrum. Comparison of multidimensional fluorescent properties of RBC under physiological-like and oxidative-stress conditions in the presence and absence of 1a suggests its dual activity as probe and singlet-oxygen generator and opens up a pathway for using FLIM to analyze complex intracellular behavior of flavin-like compounds. These new data on structure–property relationship contribute to the body of information required for a rational design of flavin-based tools for future biological and biochemical applications. [ABSTRACT FROM AUTHOR]

A photodegradation study of 5‐fluorouracil (5‐FU) has been carried out in the water (pH 7.0) and organic solvents (chloroform, ethyl acetate, acetone, 1‐butanol, 1‐propanol, ethanol, methanol, and acetonitrile) using developed and validated high‐performance liquid chromatography (HPLC) method. The test method was found to be simple, accurate (% recovery, 100.25%–101.08%), precise (%RSD < 2.00), and sensitive. The apparent first‐order rate constants are in the range of 0.85 (chloroform) to 4.25 × 10−4 min−1 (water). The values obtained for kobs were found to be linear as a function of the dielectric constant indicating the involvement of the dipolar intermediate in the reaction. The increase in the rate of degradation of this intermediate is enhanced by the polarity of the medium. Rates of photolysis for 5‐FU show a linear relationship with the solvent acceptor number (AN) which indicates the degree of solute–solvent interaction. The values of kobs were found to be linear to the inverse of the viscosity of the medium due to the diffusion‐controlled process. [ABSTRACT FROM AUTHOR]

A stability-indicating photochemical method for the assay of riboflavin (RF) in photodegraded samples and aged vitamin preparations has been developed. It is based on photochemical conversion of RF to lumichrome (LC) in alkaline solution under controlled conditions of light intensity, temperature, pH, time of exposure, and distance. Under these conditions about two-thirds of RF is converted to LC and on the basis of the RF : LC ratio the concentration of RF can be determined in degraded solutions. The method involves the extraction of photolyzed solutions of RF (pH 2.0) with chloroform and determination of LC along with lumiflavin (LF) by a two-component spectrometric method at 356 and 445 nm. The method has been validated and the results of the assay of RF in photodegraded solutions compare well with those of the standard USP fluorimetric method. The recovery of the method is 99–101% and the precision is within 2%. The method is stability-indicating and can be applied to the assay of RF in photodegraded solutions and aged vitamin preparations. The method is specific compared to that of the USP fluorimetric method in which the degraded LC may interfere with the fluorescence emission of RF. [ABSTRACT FROM AUTHOR]

Graphical abstract The photolysis of riboflavin (RF) at pH 7.0 in the presence of reducing dianions results in simultaneous photoaddition, photoreduction and chemical reduction to yield cyclodehydroriboflavin (CDRF), lumichrome (LC) and dihydroriboflavin (DHRF), respectively. The photoaddition reaction of RF is catalyzed by dianions in the order: S 2 O 5 2− > S 2 O 3 2− > SO 3 2− and the chemical reduction is enhanced in the reverse order. Highlights • Riboflavin (RF) undergoes photoaddition and photo/chemical reduction by dianioins. • Photoaddition of RF is catalyzed by dianioins in the order: S 2 O 5 2− > S 2 O 3 2− > SO 3 2−. • Chemical reduction of RF is enhanced by dianions in the order: S 2 O 3 2− > SO 3 2− > S 2 O 5 2−. • First-order rate constants for photolysis are a function of RF fluorescence loss. • Chemical reduction of RF is determined by the redox potentials of dianions. Abstract The present investigation involves the evaluation of the effect of reducing dianions (SO 3 2−, S 2 O 3 2−, S 2 O 5 2−) on the kinetics of simultaneous photoaddition, photoreduction and chemical reduction reactions of riboflavin (RF) at pH 6–8. The photoproducts of these reactions have been identified and assayed during the degradation of RF. The final products of the above reactions are cyclodehydroriboflavin (CDRF), lumichrome (LC) and dihydroriboflavin (DHRF), respectively. The first-order rate constants for the loss of RF (k obs) (0.61–3.07 × 10-3 min-1) and formation of photoproducts (0.21–1.61 × 10-3 min-1) in the presence of dianions (0.2–1.0 M), and the second-order rate constants for the photochemical interaction of RF and dianions (1.42–2.01 × 10-3 M-1 min-1) and for the chemical reduction of RF (dark) (2.31–3.25 × 10-3 M-1 min-1) have been determined. The UV and visible spectral and fluorescence characteristics of RF in the presence of dianions have been studied. The fluorescence of RF is quenched by dianions depending upon the extent of their interaction with the molecule. The photoaddition of RF is optimum under neutral pH conditions and is catalyzed by the dianions in the order: S 2 O 5 2− > SO 3 2− > S 2 O 3 2−, whereas the chemical reduction is enhanced in the reverse order. The S 2 O 3 2− dianion is most effective as a reducing agent on the basis of its redox potential which is lower than that of the SO 3 2−dianion. The quantum yields of photodegradation of RF in the presence of dianions (0.018–0.046) have been determined. The mode of photodegradation reactions of RF has been discussed. [ABSTRACT FROM AUTHOR]

Graphical abstract The formation of cyclodehydroriboflavin (CDRF) involves the interaction of riboflavin (RF) with divalent anions (e.g. CO 3 2−) to form a RF−CO 3 2− complex. This complex on excitation to singlet state 1[RF ox ] undergoes cyclization to give a dihydroflavin intermediate which on autoxidation yields CDRF. Highlights • Photolysis of riboflavin (RF) in the presence of divalent anions is highest at pH 7.0. • Carbonate, oxalate, phthalate from cyclodehydroriboflavin by RF photoaddition. • Rate of photoaddition depends on RF fluorescence quenching by divalent anions. • Divalent anions alter photoreduction pathway of RF to photoaddition pathway. • A multicomponent spectrometric method is used for the assay of RF and photoproducts. Abstract A study of the effect of some divalent anions (carbonate, oxalate, phthalate, phosphate) on the kinetics of photodegradation reactions of riboflavin (RF) and its pathways, product composition and fluorescence quenching in the pH range 6.0–8.0 has been conducted. The photodegradation of RF in the presence of 0.2–1.0 M divalent anions on visible irradiation leads to the formation of cyclodehydroriboflavin (CDRF) by photoaddition pathway and lumichrome (LC) by photoreduction pathway as the major end products. These products are formed by simultaneous first–order reactions. The divalent anions deviate the photoreduction pathway of RF in favor of photoaddition pathway to yield CDRF. The extent of this variation depends on the strength of RF–divalent anion complex as indicated by an increase in the loss of RF fluorescence due to complex formation. The first– and second–order rate constants for the photodegradation of RF have been determined and the effect of pH on the rates of these reactions evaluated. The rate of divalent anion catalyzed formation of CDRF is maximum at pH 7 and occurs in the order: carbonate > phosphate > oxalate > phthalate. The catalytic activity of the divalent anions increases with the strength of RF–divalent anion complex resulting in an increase in the rate of formation of CDRF and a decrease in the rate of formation of LC by different pathways. [ABSTRACT FROM AUTHOR]

The photolysis of methylcobalamin (MC) in aqueous solution (pH 1.0–12.0) under aerobic condition has been studied on irradiation in the visible region. It leads to the formation of aquocobalamin (B 12a ) in acid solution and hydroxocobalamin (B 12b ) in alkaline solution. This is indicated by the changes in the spectra of MC with a shift towards 525 nm in the acidic and alkaline solutions. The reaction follows first-order kinetics and the values of apparent first-order rate constants ( k obs ) using a 125 W lamp range from 2.80 (pH 12.0) to 27.25 × 10 −2  min −1 (pH 5.0). The k-pH profile for the reaction represents a bell-shaped curve with the maximum rate of photolysis around pH 5.0. The rates of the reaction decrease with a decrease in pH in the acid solution due to protonation and with an increase in pH in the alkaline solution due to ionization of the molecule. MC shows highest fluorescence around pH 5.0 with a decrease in pH in the acidic region and with an increase in pH in the alkaline region. MC and B 12a / B 12b in the irradiated solutions have been determined by a two-component spectrometric assay at 461 and 525 nm with a precision of ±2%. A reaction scheme for the photolysis of MC in aqueous solution has been presented. [ABSTRACT FROM AUTHOR]

The photodegradation of ascorbic acid (AH 2 ) in the presence of nicotinamide (NA) at pH 2.0–12.0 has been studied using a 30 W UV radiation source. The reaction follows first-order kinetics and the values of apparent first-order rate constants ( k obs ) at 1 × 10 −3  M NA concentration range from 1.17 (pH 2.0) to 3.61 × 10 −3  min −1 (pH 12.0). The values of these rate constants ( k 0 ) in the absence of NA range from 0.50 (pH 2.0) to 1.75 × 10 −3  min −1 (pH 12.0), indicating that the values of k obs for the photodegradation of AH 2 in the presence of NA are about 2 fold compared to those of the AH 2 alone. The second-order rate constants ( k ' ) for the photochemical interaction of AH 2 and NA are in the range of 0.67 (pH 2.0) and 1.86 × 10 −3  M −1  min −1 (pH 12.0). The k' -pH profile shows a gradual increase in the rate as a function of pH. This is due to the ionization of AH 2 to give ascorbyl anions (AH − ) which are more susceptible to photodegradation compared to the neutral molecule (AH 2 ). NA appears to undergo photochemical interaction with AH 2 during the reaction by acting as an electron acceptor to enhance its rate of photodegradation. The concentrations of AH 2 and NA in degraded solutions have been determined by a two-component spectrometric method at 243 and 261 nm (pH 2.0) with a precision of ±2%. The method has been validated and the results are comparable to the HPLC method. [ABSTRACT FROM AUTHOR]

In Pakistan, avian influenza surveillance has been both active and passive. Here, we present the results of a survey effort focusing solely on the live bird markets and wild bird species from different zoos and national parks to understand the impact of live bird markets on the spread of highly pathogenic avian influenza viruses. A cross sectional survey was conducted from Jan-Dec 2011 to identify and isolate the circulating avian influenza virus subtypes in live bird markets and wild birds from different localities in and around Islamabad Capital Territory. Swabs, tracheal tissues and sera samples were collected, screened and diagnosed by hemagglutination inhibition assay and RT-PCR. The highest seropositivity was recorded for H9 (100 %) followed by H5 (89.4%) and H7 (72.3%). All 27 isolates were of the low pathogenic H9N2 subtypes and no viruses could be successfully isolated of subtype H5N1 or H7N7. The higher prevalence of H5N1 (89.4%) observed in the present study was an alarming threat; therefore, we suggested immediate control strategies against this emerging risk of H5N1 for human in live bird markets in Pakistan. The factors unveiled in this study will help in understanding the lapses in controlling persistent outbreaks of avian influenza in country. [ABSTRACT FROM AUTHOR]

Liquid biopsy has gained increasing interest in the growing era of precision medicine as minimally invasive technique. Recent findings demonstrated that detecting minimal or molecular residual disease (MRD) in NSCLC is a challenging matter of debate that need multidisciplinary competencies, avoiding the overtreatment risk along with achieving a significant survival improvement. This review aims to provide practical consideration for solving data interpretation questions about MRD in NSCLC thanks to the close cooperation between biologists and oncology clinicians. We discussed with a translational approach the critical point of view from benchside, bedside and bunchside to facilitate the future applicability of liquid biopsy in this setting. Herein, we defined the clinical significance of MRD, focusing on relevant practical consideration about advantages and disadvantages, speculating on future clinical trial design and standardization of MRD technology. • Minimal residual disease (MRD) detection provides earlier cancer diagnosis, and a more accurate prediction of relapse. • MRD detection must be standardized to increase sensitivity. • Liquid biopsies hold several advantages compared to solid tissue biopsies, including being less invasive, costly, and time-consuming. • Detection of MRD could improve cancer care by allowing earlier cancer detection, better prediction of recurrence, and assessing efficacy of treatments. [ABSTRACT FROM AUTHOR]

The photolysis of riboflavin (RF) in aqueous solution in the presence of nicotinamide (NA) by visible light has been studied in the pH range 1.0-12.0 and the various photoproducts have been identified as known compounds. RF has been determined in degraded solutions by a specific multicomponent spectrometric method in the presence of its photoproducts and NA. The second-order rate constants (k2) for the bimolecular interaction of RF and NA range from 0.54 (pH 1.0) to 9.66 M-1 min-1 (pH 12.0). The log k2-pH profile for the photolysis reaction follows a sigmoid curve showing a gradual increase in the rate of pH due to a change in the ionization behavior of the molecule. The lower rate in the acid region is probably due to protonation of the molecule since the cationic form of RF is less susceptible to photolysis than the neutral form. Similarly, a slowing of the rate in the alkaline region is due to anion formation of the molecule. NA is involved as an electron acceptor during the sequence of reactions and thus enhances the rate of photolysis of RF. Absorption and fluorescence measurements did not provide evidence for the complex formation between the two compounds under the present conditions. [ABSTRACT FROM AUTHOR]

A study of the formulation of liposomal preparations of riboflavin (RF) with compositional variations in the content of phosphatidylcholine (PC) and their entrapment efficiency (26–42%) have been conducted. Light transmission characteristics of the liposomal preparations have been determined to evaluate their effect on the amount of light passing through the system to initiate a photochemical reaction. Dynamic light scattering (DLS) and atomic force microscopy (AFM) have been used to study the physical characteristics of liposomes. The liposomal preparations of RF have been subjected to photolysis using visible light and the apparent first- order rate constant, k obs , for the degradation of RF have been determined. The values of k obs (1.73–2.29 × 10 − 3 min − 1 ) have been found to decrease linearly with an increase in PC concentration in the range of 12.15 to 14.85 mM. Thus, an increase in PC concentration of liposomes leads to an increase in the stability of RF. RF and its main photoproduct, lumichrome (LC), formed in liposomes have been assayed by a two-component spectrometric method at 356 and 445 nm using an irrelevant absorption correction to compensate for the interference of liposomal components. The fluorescence measurements of RF in liposomes indicate excited singlet state quenching and the formation of a charge-transfer complex between RF and PC. It results in electron transfer from PC to RF to cause photoreduction and stabilization of RF. [ABSTRACT FROM AUTHOR]

In this study, we have performed autozygosity mapping on a large consanguineous Pakistani family segregating with intellectual disability. We identified two large regions of homozygosity-by-descent (HBD) on 16q12.2-q21 and 16q24.1-q24.3. Whole exome sequencing (WES) was performed on an affected individual from the family, but initially, no obvious mutation was detected. However, three genes within the HBD regions that were not fully captured during the WES were Sanger sequenced and we identified a five base pair deletion (actually six base pairs deleted plus one base pair inserted) in exon 7 of the gene FBXO31. The variant segregated completely in the family, in recessive fashion giving a LOD score of 3.95. This variant leads to a frameshift and a premature stop codon and truncation of the FBXO31 protein, p.(Cys283Asnfs*81). Quantification of mRNA and protein expression suggests that nonsense-mediated mRNA decay also contributes to the loss of FBXO31 protein in affected individuals. FBXO31 functions as a centrosomal E3 ubiquitin ligase, in association with SKP1 and Cullin-1, involved in ubiquitination of proteins targeted for degradation. The FBXO31/SKP1/Cullin1 complex is important for neuronal morphogenesis and axonal identity. FBXO31 also plays a role in dendrite growth and neuronal migration in developing cerebellar cortex. Our finding adds further evidence of the involvement of disruption of the protein ubiquitination pathway in intellectual disability. [ABSTRACT FROM AUTHOR]

Nonsyndromic hearing loss is a paradigm of genetic heterogeneity with 85 loci and 39 nuclear disease genes reported so far. Mutations of BSND have been shown to cause Bartter syndrome type IV, characterized by significant renal abnormalities and deafness and nonsyndromic nearing loss. We studied a Pakistani consanguineous family. Clinical examinations of affected individuals did not reveal the presence of any associated signs, which are hallmarks of the Bartter syndrome type IV. Linkage analysis identified an area of 18.36Mb shared by all affected individuals between markers D1S2706 and D1S1596. A maximum two-point LOD score of 2.55 with markers D1S2700 and multipoint LOD score of 3.42 with marker D1S1661 were obtained. BSND mutation, that is, p.I12T, cosegregated in all extant members of our pedigree. BSND mutations can cause nonsyndromic hearing loss, and it is a second report for this mutation. The respected protein, that is, BSND, was first modeled, and then, the identified mutation was further analyzed by using different bioinformatics tools; finally, this protein and its mutant was docked with CLCNKB and REN, interactions of BSND, respectively. [ABSTRACT FROM AUTHOR]

• Photochemical interaction of vitamin B 12 /B 12b in presence of cysteine (CYS) has been confirmed by spectroscopic methods. • Kinetics of photolysis of B 12 /B 12b ̶ CYS has been studied. • B 12 and B 12b ̶ CYS have been determined by spectrometric method. • The Mode of photochemical interaction of CYS and B 12 and B 12a /B 12b has been discussed. • Quantum yields of photolysis of B 12 and B 12a/b have been determined. The photolysis of cyanocobalamin (B 12) and hydroxocobalamin (B 12b) in the presence of cysteine (CYS) is investigated. The reactions follow first–order kinetics and the values of first–order constants (k obs) at pH 2.0–12.0 range from 0.82–9.25 × 10–4 min–1 and 4.93–16.40 × 10–4 min–1, for B 12 and B 12b , respectively. The second–order rate constants (k 2) for photochemical interaction of B 12 and B 12b in the presence of CYS range from 0.19 M–1 min–1 to 0.98 M–1 min–1 and 0.35 M–1 min–1to 1.65 M–1 min–1, respectively. The k 2 values of B 12b –CYS interaction are nearly twice compared to those of B 12 –CYS indicating that the B 12b –CYS has greater susceptibility towards degradation than B 12 –CYS in the pH range studied. The k 2 –pH profiles for the photodegradation of both compounds are bell–shaped showing that CYS ionization affects the rates of reaction. The degree of interaction of B 12 and B 12b with CYS is indicated by the loss of B 12 and B 12b fluorescence. The values of k obs for photolysis of B 12 and B 12b are in accordance with the fluorescence intensity of both the compounds in the whole pH range studied. Quantum yields ofB 12 /B 12b photolysis are in the range of 0.001 to 0.009 and 0.007 to 0.013, respectively. [ABSTRACT FROM AUTHOR]

Review: 164 refs. [ABSTRACT FROM AUTHOR]