Assessment of nutraceutical value, physicochemical, and anti-inflammatory profile of Odonthalia floccose and Odonthalia dentata.

The nutraceutical value, and physicochemical profile as well as anti-inflammatory activity potential of Odonthalia floccose and Odonthalia dentata (red macroalgae) dry biomass were investigated in this study. Proximate composition study results revealed that the dry biomass of O. floccose and O. dentae were found to be as ash: 9.11 & 8.7 g 100 g-1, moisture: 8.24 & 8.1 g 100 g-1, total fat: 6.9 & 7.2 g 100 g-1, protein: 24.52 & 25.6 g 100 g-1, and total carbohydrate/polysaccharides: 53.84 & 48.85 g 100 g-1 of dry weight biomass respectively. Both algae biomass contain considerable quantity of minerals (Fe, Cu, Mg, and Zn). Furthermore, the major saturated fatty acids (6.24 & 5.82 g FAME 100 g-1 of total fat of O. floccose and O. dentate) (ΣFAs) present in the test algae were stearic acid, palmitic acid, and margaric acids. O. floccose and O. dentata also contain remarkable protein composition profile that compiled with considerable quantity of essential and non-essential amino acids. The vitamins such as vitamin A, B1, B2, B3, B6, B9, C, and E of O. floccose and O. dentate biomass were also identified at sufficient quantity level. The swelling capacity (SWC), water holding capacity (WHC), and oil holding capacity (OHC) properties of O. floccose and O. dentate at various temperature conditions (25 and 37 ᵒC) were found to be 8.11 & 7.02 mL g-1 and 8.95 & 7.55 mL g-1, 5.1 & 4.87 and 4.8 & 4.1 mL g-1, as well as 2.11 & 1.81 and 1.96 & 1.89 mL g-1 respectively. Among these two marine red macroalgae samples, the O. dentate showed better anti-inflammatory activity than O. floccose at 150 µg mL-1 dosage. Thus, this O. floccose and O. dentate biomass can be considerable as nutritional supplement and pharmaceutical product development related research.

Analysis of the remediation competence of Aspergillus flavus biomass in wastewater of the dyeing industry: An in-vitro study.

The dyeing industry effluent causes severe environmental pollution and threatens the native flora and fauna. The current study aimed to analyze the physicochemical parameters of dyeing industry wastewater collected in different sites (K1, E2, S3, T4, and V5), as well as the metal tolerance and decolourisation ability of Aspergillus flavus. Furthermore, the optimal biomass quantity and temperatures required for efficient bioremediation were investigated. Approximately five dyeing industry wastewater samples (K1, E2, S3, T4, and V5) were collected from various sampling stations, and the majority of the physical and chemical characteristics were discovered to be above the permissible limits. A. flavus demonstrated outstanding metal resistance to As, Cu, Cr, Zn, Hg, Pb, Ni, and Cd on Potato Dextrose Agar (PDA) plates at concentrations of up to 500 g mL-1. At 4 g L-1 concentrations, A. flavus biomass decolorized up to 11.2-46.5%. Furthermore, 35°C was found to be the optimal temperature for efficient decolourisation of A. flavus biomass. The toxicity of 35°C-treated wastewater on V. mungo and prawn larvae was significantly reduced. These findings indicate that the biomass of A. flavus can be used to decolorize dyeing industry wastewater.

A conserved Plasmodium structural integrity maintenance protein (SIMP) is associated with sporozoite membrane and is essential for maintaining shape and infectivity.

Plasmodium sporozoites are extracellular forms introduced during mosquito bite that selectively invade mammalian hepatocytes. Sporozoites are delimited by a cell membrane that is linked to the underlying acto-myosin molecular motor. While membrane proteins with roles in motility and invasion have been well studied, very little is known about proteins that maintain the sporozoite shape. We demonstrate that in Plasmodium berghei (Pb) a conserved hypothetical gene, PBANKA_1422900 specifies sporozoite structural integrity maintenance protein (SIMP) required for maintaining the sporozoite shape and motility. Sporozoites lacking SIMP exhibited loss of regular shape, extensive membrane blebbing at multiple foci, and membrane detachment. The mutant sporozoites failed to infect hepatocytes, though the altered shape did not affect the organization of cytoskeleton or inner membrane complex (IMC). Interestingly, the components of IMC failed to extend under the membrane blebs likely suggesting that SIMP may assist in anchoring the membrane to IMC. Endogenous C-terminal HA tagging localized SIMP to membrane and revealed the C-terminus of the protein to be extracellular. Since SIMP is highly conserved among Plasmodium species, these findings have important implications for utilizing it as a novel sporozoite-specific vaccine candidate.

Implications of genetic variations, differential gene expression, and allele-specific expression on metformin response in drug-naïve type 2 diabetes.

PURPOSE: Metformin is widely used to treat type 2 diabetes mellitus (T2DM) individuals. Clinically, inter-individual variability of metformin response is of significant concern and is under interrogation. In this study, a targeted exome and whole transcriptome analysis were performed to identify predictive biomarkers of metformin response in drug-naïve T2DM individuals. METHODS: The study followed a prospective study design. Drug-naïve T2DM individuals (n = 192) and controls (n = 223) were enrolled. T2DM individuals were administered with metformin monotherapy and defined as responders and non-responders based on their glycated haemoglobin change over three months. 146 T2DM individuals were used for the final analysis and remaining samples were lost during the follow-up. Target exome sequencing and RNA-seq was performed to analyze genetic and transcriptome profile. The selected SNPs were validated by genotyping and allele specific gene expression using the TaqMan assay. The gene prioritization, enrichment analysis, drug-gene interactions, disease-gene association, and correlation analysis were performed using various tools and databases. RESULTS: rs1050152 and rs272893 in SLC22A4 were associated with improved response to metformin. The copy number loss was observed in PPARGC1A in the non-responders. The expression analysis highlighted potential differentially expressed targets for predicting metformin response (n = 35) and T2DM (n = 14). The expression of GDF15, TWISTNB, and RPL36A genes showed a maximum correlation with the change in HbA1c levels. The disease-gene association analysis highlighted MAGI2 rs113805659 to be linked with T2DM. CONCLUSION: The results provide evidence for the genetic variations, perturbed transcriptome, allele-specific gene expression, and pathways associated with metformin drug response in T2DM.

Disposal of obsolete mobile phones: A review on replacement, disposal methods, in-use lifespan, reuse and recycling.

Usage/consumption of mobile phones has increased rapidly around the world. As of April 2021, there were 5.27 billion mobile phone users. Meanwhile, the generation of obsolete mobile phones/mobile phone wastes is also increased mainly due to the replacement of mobile phones. The in-use lifespan of mobile phones is correspondingly getting decreased. The inappropriate disposal of obsolete mobile phones leads to adverse consequences on the environment, human health and on metal recovery. This review article provides an insight on findings from various articles on disposal of obsolete mobile phones by users/consumers. The various aspects, such as reasons for replacement, disposal methods adopted by users/consumers, impact due to the adoption of improper disposal methods such as handing them over to the informal recycling sector and storage/hibernation after its in-use lifespan, were covered. Along with this, the study even focuses on reduce, reuse and recycle (3Rs) of sustainability. Reduce means reduction of mobile phone replacement frequency. Storage of mobile phones post-in-use lifespan is the most opted disposal method, and it is one of the significant barriers to reuse, recycling and metal recovery. When it comes to recycling, the research undertaken on the recycling of obsolete mobile phones is not as in-depth when compared to the research done on recycling of e-waste in general. This article identifies future directions for sustainable end-of-life management of obsolete mobile phones.

CT imaging patterns of paraduodenal pancreatitis: a unique clinicoradiological entity.

AIM: To analyse the computed tomography (CT) findings of paraduodenal pancreatitis (PP) in patients treated at Amrita Institute of Medical Sciences. MATERIALS AND METHODS: Clinical, laboratory, and CT findings of 30 patients with PP treated from July 2007 to December 2020 were reviewed retrospectively. RESULTS: The average age of the patients was 45.9 years (19-60 years), which included 29 (96.7%) men, and 90% had a history of alcohol abuse. The majority [22 (73.3%)] presented with recurrent abdominal pain. Serum amylase was elevated in 21 (70%) patients and serum lipase was elevated in 25 (83.3%) patients. Carbohydrate antigen (CA 19-9) was elevated in three (10%) patients. The cystic pattern was seen in three (10%), solid pattern in 13 (43.3%), and solid-cystic pattern in 14 (46.7%) patients. The pure form of the disease was seen in seven (23.3%) patients, whereas the segmental form was seen in 23 (76.7%) patients. Descending duodenal wall thickening and enhancement was seen in 25 (83.3%) and 18 (60%) patients, respectively. The gastroduodenal artery was displaced medially in 12 (40%) patients and encased in five (16.7%) patients; however, it was not occluded in any of the patients. Calcifications were seen in the groove lesion in nine (30%) patients. The pancreas showed atrophic changes in 14 (46.6%) patients and calcifications in 12 (40%) patients. Distal common bile duct strictures were seen in three (10%) patients. CONCLUSIONS: The presence of sheet-like soft-tissue thickening in the groove with diffuse duodenal thickening and intramural/paraduodenal cysts are highly suggestive of PP. Identifying characteristic imaging findings of PP may help in prospective diagnosis and lead to conservative management of most of these patients avoiding unnecessary invasive procedures.

Influence of AS-7 on the storage lesion in young and old circulating erythrocytes.

Blood and its components are stored to meet the demands of blood transfusion. Erythrocytes undergo progressive modifications during storage known as storage lesions. Storage solutions were developed to improve shelf life and extend red cell viability. Therefore, the objective of this study is to analyze the effects of AS-7 on young and old erythrocytes during storage. Blood was collected from the blood bank at Kempegowda Institute of Medical Sciences (KIMS) hospital, Bengaluru. Erythrocytes were isolated from whole blood and separated based on its age using Percoll density gradient. The young and old erythrocytes were stored in AS-7 for 35 days and every 5th day, oxidative stress markers - Hemoglobin (Hb), Oxidative Hemolysis, Mechanical Fragility, Sialic Acid, Superoxides, Glucose, Lactate Dehydrogenase (LDH), Glutathione, antioxidant capacity (TACCUPRAC), Plasma Membrane Redox System (PMRS), antioxidant enzymes, lipid peroxidation, and protein oxidation products were assessed. Hb, glucose, TACCUPRAC, and superoxide dismutase reduced, while oxidative hemolysis, mechanical fragility, protein oxidation, and lipid peroxidation products increased in young and old cells over storage. LDH, PMRS, catalase, advanced oxidation protein products, and conjugate dienes were significant in old cells from day 5 itself, whereas in young cells towards the end of storage (from day 25). Oxidative insult was higher in old cells compared to young cells. AS-7 was beneficial to young erythrocytes during storage and thus laying the foundation for the possibilities of utilizing young cells as models for storage studies.

Age-Related Modulations in Erythrocytes under Blood Bank Conditions.

BACKGROUND: During storage of erythrocytes, storage lesions are formed that reduce the safety and efficacy of the stored blood. Thus, there is a need to understand the changes that occur during storage. Most studies have focused on storage of a mixed population of erythrocytes. The aim of this study is to analyze the changes in young and old erythrocytes over the course if storage. MATERIALS AND METHODS: Blood was collected from the blood bank at the Kempegowda Institute of Medical Sciences (KIMS) Hospital (Bengaluru, India) and stored for 35 days in CPDA-1 at 4°C. Every 5 days, erythrocytes were separated based on the blood's age using a Percoll-BSA gradient. Young and old erythrocytes obtained were used for analysis of the following oxidative stress (OS) markers: hemoglobin (Hb), hemolysis, mechanical fragility, antioxidant enzymes (superoxide dismutase and catalase [CAT]), superoxides, sialic acid, glutamic oxaloacetate transaminase (GOT), glucose, plasma membrane redox system (PMRS), total antioxidant capacity-cupric ion reducing antioxidant capacity assay (TACCUPRAC), lactate dehydrogenase (LDH), lipid peroxidation products (malondialdehyde [MDA] and conjugate dienes), and protein oxidation products (advanced oxidation protein products and protein sulfhydryls). RESULT: Young cells had higher amounts of Hb, sialic acid, GOT, LDH, TACCUPRAC, CAT, and superoxides compared to old cells. Old cells, however, had higher PMRS and MDA levels with respect to young cells. DISCUSSION: Young cells could endure OS during storage more efficiently than old cells. In conclusion, the efficacy of stored blood depends on the ratio of young cells in the population. This study highlights the prospects of storing young erythrocytes for a prolonged shelf life of blood.

Binding orientation and interaction of bile salt in its ternary complex with pancreatic lipase-colipase system.

The interfacial activity of pancreatic lipases (PL) depends on the presence of colipase and bile salt. The activity of PL is inhibited by micellar concentrations of bile salt which can be restored by the addition of colipase. Though the formation of 1:1:1 tertiary complex by lipase-colipase-bile salt micelle is well accepted, the residue-level interactions between lipase-colipase and bile salt are yet to be clearly understood. Molecular dynamic simulations of lipase-colipase complex, lipase and colipase were performed in the presence of a model bile salt, sodium taurocholate (NaTC), at its near-CMC and supra-micellar concentrations. From the interactions obtained from the molecular dynamic simulations, the ternary complex was modelled and compared with earlier reports. The analysis suggested that a micelle of NaTC consisting of nine monomers was formed at the concave groove between lipase and colipase chain and it mainly interacted with the fourth finger of colipase. This complex was mainly stabilized by van der Waals interactions. Interestingly, the C-terminal domain of lipase which holds the colipase did not show any significant role in formation or stabilization of NaTC micelle.

Lid dynamics of porcine pancreatic lipase in non-aqueous solvents.

BACKGROUND: Understanding the dynamics of enzymes in organic solvents has wider implications on their industrial applications. Pancreatic lipases, which show activity in their lid open-state, demonstrate enhanced activity in organic solvents at higher temperatures. However, the lid dynamics of pancreatic lipases in non-aqueous environment is yet to be clearly understood. METHODS: Dynamics of porcine pancreatic lipase (PPL) in open and closed conformations was followed in ethanol, toluene, and octanol using molecular simulation methods. In silico double mutant D250V and E254L of PPL (PPLmut-Cl) was created and its lid opening dynamics in water and in octanol was analyzed. RESULTS: PPL showed increase in solvent accessible surface area and decrease in packing density as the polarity of the surrounded solvent decreased. Breaking the interactions between D250-Y115, and D250-E254 in PPLmut-Cl directed the lid to attain open-state conformation. Major energy barriers during the lid movement in water and in octanol were identified. Also, the trajectories of lid movement were found to be different in these solvents. CONCLUSIONS: Only the double mutant at higher temperature showed lid opening movement suggesting the essential role of the three residues in holding the lid in closed conformation. The lid opening dynamics was faster in octanol than water suggesting that non-polar solvents favor open conformation of the lid. GENERAL SIGNIFICANCE: This study identifies important interactions between the lid and the residues in domain 1 which possibly keeps the lid in closed conformation. Also, it explains the rearrangements of residue-residue interactions during lid opening movement in water and in octanol.

Lid closure dynamics of porcine pancreatic lipase in aqueous solution.

BACKGROUND: Pancreatic lipases hydrolyze fatty acids in dietary pathway. The activity of porcine pancreatic lipase (PPL) is controlled by lid domain along with a coenzyme, colipase. The active open-state conformation of the protein could be induced by detergents or bile salts which would be further stabilized by binding of colipase. In the absence of these interactions, the lid preferably attains a closed conformation in water. METHODS: Molecular dynamic simulation was used to monitor the lid movement of PPL in open and closed conformations in water. Free energy surface was constructed from the simulation. Energy barriers and major structural changes during lid opening were evaluated. RESULTS: The lid closure of PPL in water from its open conformation might be initiated by columbic interactions which initially move the lid away from domain 1. This is followed by major dihedral changes on the lid residues which alter the trajectory of motion. The lid then swirls back towards domain 1 to attain closed conformation. This is accompanied with conformational changes around ß5- and ß9-loops as well. However, PPL in closed conformation shows only the domain movements and the lid remains in its closed conformation. CONCLUSIONS: PPL in closed conformation is stable in water and the open conformation is driven towards closed state. The lid follows a swirling trajectory during the closure. GENERAL SIGNIFICANCE: Conformational state of the lid regulates the activity and substrate specificity of PPL. Hence, it is essential to understand the lid dynamics and the role of specific amino acid residues involved.

Bio-prospecting of coral (Porites lutea) mucus associated bacteria, Palk Bay reefs, Southeast coast of India.

Coral mucus is one of the key localization in the coral holobiont, as this serves as an energy rich substrate for a wide range of abundant, diverse and multifunctional microbiota. However, very little is known about the functional role of bacterial communities in their associations with corals. In the present study, a total of 48 isolates were obtained from Porites lutea wherein the genus of Bacillus sp. and Vibrio sp. were predominant. Bio-prospecting the coral mucus revealed the existence of (10.42%) antagonistic bacteria against the tested bacterial pathogens. Molecular taxonomy (16S rRNA) proved the identity of these antagonistic bacteria belong to Enterobacter cloacae (CM1), Bacillus subtilis (CM2), Bacillus sp. (CM11) and Bacillus marisflavi (CM12). The secondary screening emphasized that the ethyl acetate extract of B. subtilis showed strong antagonistic effect, followed by the chloroform extract of E. cloacae and ethyl acetate extract of B. marisflavi. The antagonistic activity was statistically confirmed by Principal Component Analysis and Hierarchical Cluster Analysis. The privileged coral mucus associated bacterial (CMAB) solvent extracts inhibited the bacterial pathogens at 100 µg/ml (MIC) and ceased the growth at 200 µg/ml (MBC). The hemolytic and brine shrimp lethality assays disclosed the non-toxic nature of solvent extracts of CMAB. Altogether, the present investigation brought out the diversity of bacteria associated with the mucus of P. lutea. In addition, bio-prospecting corroborated the CMAB as the potential source of pharmacologically important bioactive compounds against a wide range of bacterial pathogens.

Analysing the microenvironment of 2-p-toluidinylnaphthalene-6-sulfonate (TNS) in solvents and in different conformational states of proteins in relation to its fluorescence properties: a computational study.

Characterization of different conformational states of proteins is essential to understand their stability and activity. Biophysical techniques aid in analysing these conformational states and molecular fluorescence is one of the most reliable and quickly accessible methods. Apart from the intrinsic fluorescence of proteins, external fluorescence dyes such as TNS, ANS, nile red and thioflavin are also used to characterize partially unfolded, aggregated and fibrillar states of proteins, though their exact molecular-level interactions with proteins are yet to be completely unravelled. The present study attempts to investigate the binding of TNS molecules on different conformational states of proteins. Unconstrained molecular dynamics simulation of 50 molecules of TNS with the native state of BSA, native and two partially unfolded states of RNase A and α-lactalbumin in water was carried out. Dynamics simulation of TNS alone in different solvents such as water, ethanol, DMF and DMSO was also performed. Binding environments in all the proteins and the solvents were analysed in terms of H-bonding interactions, order of contacts, amino acid specificity and conformational changes of TNS, and correlated with experimentally observed fluorescence changes of the dye. The results suggest that TNS forms aggregates in water whereas in non-aqueous solvents the order of aggregates is lower which might result in an enhancement of its fluorescence intensity. Further, TNS preferably interacts with basic and aromatic amino acid residues of the proteins. In RNase A and α-lactalbumin, most of the TNS molecules tend to form aggregates even with the unfolded conformations of the proteins. However in BSA, the number of aggregated TNS molecules is less and TNS molecules in monomeric form are found in the hydrophobic crevices of the protein. This might result in an enhancement of the fluorescence in BSA compared to the other proteins. The distributions of angles and dihedrals of TNS in different environments suggest that the bending movement between the naphthyl and tolyl rings is constrained whereas significant planar rotations could be observed both in solvents and in protein-bound states.

Biocompatibility and antibacterial activity of the Adathoda vasica Linn extract mediated silver nanoparticles.

The aim of this study is to investigate the biocompatibility and anti-Vibrio efficacy of green synthesized silver nanoparticles (AgNPs) using an aqueous leaf extract of Adathoda vasica (A. vasica). The green synthesized silver nanoparticles were characterized by UV-vis, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). A. vasica AgNPs showed significant antibacterial activity against Vibrio parahaemolyticus in agar bioassay and well diffusion method. Further, nanoparticles interactions with bacteria and its antibacterial activity were confirmed by CLSM analysis. In vivo evaluation results confirmed that synthesized A. vasica AgNPs had good antibacterial efficacy and also nontoxic to the Artemia nauplii.

Biocatalytic and antibacterial visualization of green synthesized silver nanoparticles using Hemidesmus indicus.

In the present investigation, we described the green synthesis of silver nanoparticles using plant leaf extract of Hemidesmus indicus. The synthesized silver nanoparticles were characterized by UV-visible spectroscopy, fourier transform infra-red spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). TEM images proved that the synthesized silver nanoparticles were spherical in shape with an average particle size of 25.24 nm. To evaluate antibacterial efficacy, bacteria was isolated from poultry gut and subjected to 16S rRNA characterization and confirmed as Shigella sonnei. The in vitro antibacterial efficacy of synthesized silver nanoparticles was studied by agar bioassay, well diffusion and confocal laser scanning microscopy (CLSM) assay. The H. indicus mediated synthesis of silver nanoparticles shows rapid synthesis and higher inhibitory activity (34 ± 0.2 mm) against isolated bacteria S. sonnei at 40 µg/ml.

Differential effects of ionic and non-ionic surfactants on lysozyme fibrillation.

Fibril formation is a common property of many proteins, though not all are associated with diseases. Protein surface charges and the added co-solvents play vital roles in determining fibrillation pathways and kinetics. In order to understand these phenomena, the effects of anionic, cationic and non-ionic surfactants on lysozyme fibrillation were studied. Lysozyme forms fibrils in 2 M and 4 M urea solutions following nucleation-dependent and nucleation-independent pathways, respectively, at neutral pH. Under these conditions, the effects of sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and triton X-100 (Tx) were investigated on the lysozyme structure and fibrillation. The results indicate that there are differential effects of ionic and non-ionic surfactants on fibrillation. In the presence of SDS and CTAB, above their critical micelle concentrations (CMC), lysozyme could not form fibrils. However, non-ionic Tx does not inhibit fibril formation at all concentrations. Note that the time for complete fibril formation is increased by Tx. All of the surfactants are found to increase the initial nucleation phase; however, the extent of increase is less at near the CMC of the ionic surfactants and at above the CMC of Tx. The rates of fibril elongation show varying effects in the presence of different surfactants. The results suggest that the nucleation phase of lysozyme fibrillation is primarily controlled by charge interactions and micellation of the surfactants, but multiple factors might influence the fibril elongation. Furthermore, the surfactants do not alter the fibrillation pathway from nucleation-dependent to nucleation-independent or vice versa in the studied conditions.

An empirical investigation to understand mobile phone users' behavioural intention to give their end-of-life mobile phones for formal recycling.

Mobile phones have turned into a highly essential device for numerous individuals. Swift innovation and decrease in in-use lifespan have increased the generation of end-of-life mobile phones (EOL-MPs). Lesser formal recycling of EOL-MPs has detrimental outcomes on the environment, human health, and circular economy. Therefore, this research was undertaken to investigate factors impacting mobile phone users' behavioural intention to give their EOL-MPs for formal recycling. The conceptual model was developed by integrating the theory of planned behaviour, norm activation model, and value-belief-norm theory. Responses were collected from mobile phone users aged 18 and above residing in Bengaluru, Mangaluru, and Huballi-Dharvad cities of Karnataka state, India. 1135 responses were analysed by applying partial least squares structural equation modelling. Incentives was figured out to be the most positively impacting construct on behavioural intention. Followed by awareness of consequences, social media, past recycling experience, and recycling attitude. Whereas risk perception regarding information security and convenience of recycling negatively impacts behavioural intention. Personal norms get activated by awareness of consequences and ascription of responsibility. As a result, personal norms positively impact behavioural intention. In addition, biospheric values also positively impact personal norms. The outcomes of PLSpredict signify that the conceptual model has high out-of-sample predictive power. The outcomes of this research can be utilized by various stakeholders like e-waste collection organisations, e-waste recycling organisations, mobile phone manufacturing companies, city corporations, educational institutions, etc for improving sustainable end-of-life management of EOL-MPs.

Breastfeeding and introduction of complementary foods during infancy in relation to the risk of asthma and atopic diseases up to 10 years.

BACKGROUND: It has been hypothesized that changes in diet during early life may have contributed to the increase in childhood asthma and atopy. The long-term effect of the timing and content of infant feeding on the incidence of asthma and atopic diseases in children is unclear. OBJECTIVE: To investigate the associations between duration of breastfeeding and the timing of introduction of complementary foods during the first 6 months and parental-reported asthma, wheeze and atopic eczema up to 10 years of age. METHODS: Infant feeding practices (breastfeeding and introduction of complementary foods) of 1924 singleton children participating in the Study of Eczema and Asthma To Observe the influence of Nutrition (SEATON) birth cohort were prospectively collected up to 6 months with outcomes (wheeze, atopic eczema and asthma) being assessed at 1, 2, 5 and 10 years. Data were analysed using generalized estimating equations and discrete hazards models with adjustment for confounders. RESULTS: By 6 months, 59% and 35% of mothers had stopped exclusive and total breastfeeding, respectively. Although formula feeding was adversely associated with wheeze in the past 12 months (adjusted OR for no formula feeding: 070, 95% CI 0.50-0.97), and the introduction of biscuits/bread after 5 months of age adversely associated with atopic eczema (adjusted OR 1.34, 95% CI 1.06-1.69), these results lost their statistical significance after adjustment for multiple testing. Stratification of the results by the presence of eczema by 6 months of age and family atopic history did not substantially differ from the results of the whole study population. CONCLUSION AND CLINICAL RELEVANCE: Our results suggest that the nature of infant feeding during the first 6 months seems not to substantially influence the long-term risk of asthma and atopic diseases in children, nor in children at high risk of atopic disease because of a family history of atopic disease.

Review on the interactions between dopamine metabolites and α-Synuclein in causing Parkinson's disease.

Parkinson's disease (PD) is characterized by an abnormal post-translational modifications (PTM) in amino acid sequence and aggregation of alpha-synuclein (α-Syn) protein. It is generally believed that dopamine (DA) metabolite in dopaminergic (DAergic) neurons promotes the aggregation of toxic α-Syn oligomers and protofibrils, whereas DA inhibits the formation of toxic fibers and even degrades the toxic fibers. Therefore, the study on interaction between DA metabolites and α-Syn oligomers is one of the current hot topics in neuroscience, because this effect may have direct relevance to the selective DAergic neuron loss in PD. Several mechanisms have been reported for DA metabolites induced α-Syn oligomers viz. i) The reactive oxygen species (ROS) released during the auto-oxidation or enzymatic oxidation of DA changes the structure of α-Syn by the oxidation of amino acid residue leading to misfolding, ii) The oxidized DA metabolites directly interact with α-Syn through covalent or non-covalent bonding leading to the formation of oligomers, iii) DA interacts with lipid or autophagy related proteins to decreases the degradation efficiency of α-Syn aggregates. However, there is no clear-cut mechanism proposed for the interaction between DA and α-Syn. However, it is believed that the lysine (Lys) side chain of α-Syn sequence is the initial trigger site for the oligomer formation. Herein, we review different chemical mechanism involved during the interaction of Lys side chain of α-Syn with DA metabolites such as dopamine-o-quinone (DAQ), dopamine-chrome (DAC), dopamine-aldehyde (DOPAL) and neuromelanin. This review also provides the promotive effect of divalent Cu2+ ions on DA metabolites induced α-Syn oligomers and its inhibition effect by antioxidant glutathione (GSH).

Outcome of access sphincterotomy using a needle knife converted from a standard biliary sphincterotome.

Cannulation fails in up to 10 % of all endoscopic retrograde cholangiopancreatographies (ERCPs). A standard sphincterotome can be converted to a needle knife to perform precut sphincterotomy (PCS). In this retrospective study, we analyzed cannulation rates, adverse events, and the percentage of patients requiring a second sphincterotome using a converted needle knife. Over a 7-year period, 3322 ERCPs were performed by one experienced therapeutic endoscopist; 1487 sphincterotomies were performed, 78 precut sphincterotomies using a converted needle knife. Successful cannulation using the converted needle knife was achieved in 96 % of cases at the initial procedure. Adverse events occurred in 17 % and post-ERCP pancreatitis was reported in 10 % of patients. A second sphincterotome was needed in 13 % of cases. This study shows a converted needle knife can be used for successful cannulation of either the biliary or the pancreatic duct after a failed cannulation with a standard sphincterotome, with a low percentage of adverse events anda reduction in the need for accessories.