Background
India has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) ...with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to <15 years and established a hospital-based sentinel surveillance for CRS. Reliable data about incidence of CRS is necessary to monitor progress towards the elimination goal.
Methods
We conducted serosurveys in 2019–20 among pregnant women attending antenatal clinics of 6 hospitals, which were also sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella. We systematically sampled 1800 women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We used rubella seroprevalence data from the current survey and the survey conducted in 2017 among antenatal women from another 6 CRS surveillance sites to construct a catalytic models to estimate the incidence and burden of CRS.
Result
The seroprevalence of rubella antibodies was 82.3% (95% CI: 80.4–84.0). Rubella seropositivity did not differ by age group and educational status. Based on the constant and age-dependent force of infection models, we estimated that the annual incidence of CRS in India was 225.58 per 100,000 live births (95% CI: 217.49–232.41) and 65.47 per 100,000 live births (95% CI: 41.60–104.16) respectively. This translated to an estimated 14,520 (95% CI: 9,225–23,100) and 50,028 (95% CI: 48,234–51,543) infants with CRS every year based on age-dependent and constant force of infection models respectively.
Conclusions
Our findings indicated that about one fifth of women in the reproductive age group in India were susceptible for rubella. The estimates of CRS incidence will serve as a baseline to monitor the impact of MRCV SIAs, as well progress towards the elimination goal of rubella/CRS.
The spectroscopic (FT-IR, FT-Raman, NMR), electronic (UV–-Vis.), structural and thermodynamical properties of an anti-inflammatory analgesic called Naproxen Sodium, ...(s)-6-methoxy-α-methyl-2-naphthaleneacetic acid sodium salt are submitted by using both experimental techniques and theoretical methods as quantum chemical calculations in this work. The equilibrium geometry and vibrational spectra are calculated by using DFT (B3LYP) with 6–311++G (d,p) basis set using GAUSSIAN 09. The vibrational wavenumbers are also corrected with scale factor to take better results for the calculated data. The HOMO-LUMO calculations are carried out on the title compound. The theoretical and experimental NMR peaks were found to be in good agreement. In addition, the detailed study on the Non-Bonding Orbitals, the excitation energies, AIM charges, condensed fukui calculations, thermodynamical properties, Localized Orbital Locator (LOL) and Electron Localization Function (ELF) are also performed. Furthermore, the study is extended to calculate the first order hyperpolarizability and to predict its NLO properties. The docking studies details helped on predicting the binding with different proteins.
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•FT-IR, FT-Raman, UV, NMR results were compared with theoretical data obtained using DFT B3LYP/6–311++G(d,p) basis set.•HOMO-LUMO calculations shows small energy gap for the molecule.•LOL, ELF, AIM analysis and fukui calculation were done to study nucleophilic and electrophilic sites.•NLO property was predicted and NBO studies were carried out.•Molecular docking studies predicted that compound can be used to treat blood clots in human beings.
The effect of
Lactiplantibacillus plantarum
PGB02 isolated from buttermilk on serum cholesterol profile of normal and hypercholesterolemic mice was evaluated. Further changes in the expression of ...mice genes were determined. The hypercholesterolemia was induced in experimental mice by feeding high cholesterol and fat diet. Serum cholesterol parameters, physical parameters, cholic acid excretion, and cholesterol metabolism related gene expression analysis was carried out.
L. plantarum
PGB02 efficiently reduced total cholesterol, triglycerides, and LDL-cholesterol and improved HDL-cholesterol in hypercholesterolaemic mice. Body weight was reduced and fecal cholic acid increased in probiotic treatment groups. Gene expression analysis revealed that
L. plantarum
PGB02 up-regulated the expression of LDL receptors, CYP7A1, ABCA1, ABCG5, ABCG8, and down-regulated the expression of FXR and NPC1L1 genes. Summarizing the mechanism,
L. plantarum
PGB02 improved hypercholesterolemia by increasing bile acid synthesis and excretion, reducing exogeneous cholesterol absorption from the intestine, and increased LDL clearance through upregulation of LDL-receptors. The present study has given insight into the mechanism of serum cholesterol reduction by bile salt hydrolase positive
L. plantarum
PGB02 in mice.
L. plantarum
PGB02 reduced the serum cholesterol level through increased bile acid synthesis and deconjugation and reduced absorption of cholesterol in the intestine. Isolate PGB02 shown cholesterol removal potential as good as statin.
The phosphatidylinositol 3-kinase (PI3K)/AKT and RAS oncogenic signalling modules are frequently mutated in sporadic human cancer. Although each of these pathways has been shown to play critical ...roles in driving tumour growth and proliferation, their activation in normal human cells can also promote cell senescence. Although the mechanisms mediating RAS-induced senescence have been well characterised, those controlling PI3K/AKT-induced senescence are poorly understood. Here we show that PI3K/AKT pathway activation in response to phosphatase and tensin homolog (PTEN) knockdown, mutant PI3K, catalytic, α polypeptide (PIK3CA) or activated AKT expression, promotes accumulation of p53 and p21, increases cell size and induces senescence-associated β-galactosidase activity. We demonstrate that AKT-induced senescence is p53-dependent and is characterised by mTORC1-dependent regulation of p53 translation and stabilisation of p53 protein following nucleolar localisation and inactivation of MDM2. The underlying mechanisms of RAS and AKT-induced senescence appear to be distinct, demonstrating that different mediators of senescence may be deregulated during transformation by specific oncogenes. Unlike RAS, AKT promotes rapid proliferative arrest in the absence of a hyperproliferative phase or DNA damage, indicating that inactivation of the senescence response is critical at the early stages of PI3K/AKT-driven tumourigenesis. Furthermore, our data imply that chronic activation of AKT signalling provides selective pressure for the loss of p53 function, consistent with observations that PTEN or PIK3CA mutations are significantly associated with p53 mutation in a number of human tumour types. Importantly, the demonstration that mTORC1 is an essential mediator of AKT-induced senescence raises the possibility that targeting mTORC1 in tumours with activated PI3K/AKT signalling may exert unexpected detrimental effects due to inactivation of a senescence brake on potential cancer-initiating cells.
Abstract
Aging populations and the increase in chronic diseases worldwide demand efficient healthcare tools for simple, rapid, and accurate diagnosis and monitoring the human health. In this context, ...gas sensors are used to analyze the type of gas in the breath to diagnose chronic diseases. Metal oxide and ceramic nanofibers (NFs) produced by the electrospinning (ES) method have been investigated for potential use as gas sensors in the engineering and medical sectors. The material and process parameters are the main influencing factors on the functional performance of electrospun metal oxide NFs. Zinc oxide (ZnO) based NFs are used in various gas sensors due to the wide band gap (3.37eV), large exciton binding energy, and high mobility of charge carriers of ZnO. In this research, we made an attempt to study the effect of poly(vinyl alcohol) (PVA) and zinc acetate dihydrate (ZnAc
2
) concentrations and feed rate, voltage, spinneret tip-to-collector distance (TCD), and pyrolysis temperature on the physical properties of ZnO NFs. An average fiber diameter of 119 nm was obtained after pyrolysis at 600 °C of electrospun fiber produced from an aqueous PVA solution of concentration 15 w% with 7.5 w% ZnAc
2
based on the weight of PVA. The grain size, transmittance, structural defects, and band gap energy of NFs were found to increase as a function of the pyrolysis temperature, which could be beneficial for the functional applications of these NFs.
Introduction
The therapeutic use of lithium in bipolar disorder is often restricted due to its narrow therapeutic window and adverse drug reactions. Lithium-induced early renal dysfunction is ...clinically important as it may lead to sodium depletion due to natriuresis leading to lithium retention and lithium toxicity. This is most often seen in the initial phases of therapy, and psychiatrists struggle titrating the dose of lithium and stabilizing the serum lithium level.
Objectives
The present study was conducted to evaluate the effect of add-on sodium chloride on serum lithium levels in bipolar disorder.
Methods
The present randomized controlled trial (NCT04222816) was conducted in 60 patients with type I bipolar disorder who were randomized into the control group who received lithium carbonate with the advice not to take additional salt (at the table) and the test group who received sachets of sodium chloride (1 g/d) as an add-on to lithium carbonate and were advised to restrict their additional salt intake (at the table) to 1 g/d. After baseline assessments, all patients were followed up at 4 weeks, 8 weeks, and 12 weeks when serum lithium, sodium and potassium were estimated. Serum creatinine and aldosterone were repeated at 12 weeks.
Results
In the test group, the fluctuation rate in serum lithium (26.7%) was significantly (p=0.01) lower than in the control group (63.3%). There was a significant difference in serum lithium in the control group at different time points; however, the changes were not significant in the test group. There was a significant difference in serum lithium between the groups at 8 and 12 weeks of follow-up. There were no significant differences in the change in serum sodium, potassium, creatinine, aldosterone, creatinine clearance, and blood pressure within the group and between the groups. A significant positive correlation was found between serum lithium and aldosterone at baseline.
Conclusions
Intake of add-on sodium chloride (1 gm/day) may reduce the fluctuations in serum lithium during the maintenance phase of lithium therapy in type I bipolar disorder.
Disclosure of Interest
None Declared
Summary
We compared the McGrath® Series 5 videolaryngoscope with the Macintosh laryngoscope in a simulated difficult airway, using manual in‐line stabilisation in 88 anaesthestised patients of ASA ...physical status 1‐2. The primary outcome was laryngoscopic view. Secondary outcomes included rates of successful tracheal intubation and complications. A Cormack and Lehane grade‐1 or ‐2 view was found in all patients when using the McGrath compared with 45 (51%, p < 0.0001) using the Macintosh laryngoscopes. The mean (SD) percentage of glottic opening was 82 (23)% using the McGrath compared with 13 (23)% using the Macintosh (p < 0.0001). In 66 out of 88 patients (75%), the McGrath improved the glottic view by one to three grades compared with the Macintosh (p < 0.001). Intubation of the trachea was successful in all patients using the McGrath, while the Macintosh was successful in 26 (59%, p < 0.001). There was no significant difference in the complication rates between the devices.
Despite the important roles played by ventricular fibroblasts and myofibroblasts in the formation and maintenance of the extracellular matrix, neither the ionic basis for membrane potential nor the ...effect of modulating membrane potential on function has been analyzed in detail. In this study, whole cell patch-clamp experiments were done using ventricular fibroblasts and myofibroblasts. Time- and voltage-dependent outward K(+) currents were recorded at depolarized potentials, and an inwardly rectifying K(+) (Kir) current was recorded near the resting membrane potential (RMP) and at more hyperpolarized potentials. The apparent reversal potential of Kir currents shifted to more positive potentials as the external K(+) concentration (K(+)(o)) was raised, and this Kir current was blocked by 100-300 muM Ba(2+). RT-PCR measurements showed that mRNA for Kir2.1 was expressed. Accordingly, we conclude that Kir current is a primary determinant of RMP in both fibroblasts and myofibroblasts. Changes in K(+)(o) influenced fibroblast membrane potential as well as proliferation and contractile functions. Recordings made with a voltage-sensitive dye, DiBAC(3)(4), showed that 1.5 mM K(+)(o) resulted in a hyperpolarization, whereas 20 mM K(+)(o) produced a depolarization. Low K(+)(o) (1.5 mM) enhanced myofibroblast number relative to control (5.4 mM K(+)(o)). In contrast, 20 mM K(+)(o) resulted in a significant reduction in myofibroblast number. In separate assays, 20 mM K(+)(o) significantly enhanced contraction of collagen I gels seeded with myofibroblasts compared with control mechanical activity in 5.4 mM K(+)(o). In combination, these results show that ventricular fibroblasts and myofibroblasts express a variety of K(+) channel alpha-subunits and demonstrate that Kir current can modulate RMP and alter essential physiological functions.
Parkinson's disease (PD) is a complex neurodegenerative disorder influenced by a combination of genetic and environmental factors. The molecular mechanisms that underlie PD are unknown; however, ...oxidative stress and impairment of antioxidant defence mechanisms have been implicated as major contributors to disease pathogenesis. Previously, we have reported a PD patient-derived cellular model generated from biopsies of the olfactory mucosa, termed hONS cells, in which the NRF2-mediated antioxidant response pathway genes were among the most differentially-expressed. To date, few studies have examined the role of the NRF2 encoding gene, NFE2L2, and PD. In this study, we comprehensibly assessed whether rare and common NFE2L2 genetic variations modify susceptibility to PD using a large Australian case-control sample (PD=1338, controls=1379). We employed a haplotype-tagging approach that identified an association with the tagging SNP rs2364725 and PD (OR = 0.849 (0.760-0.948), P = 0.004). Further genetic screening in hONS cell lines produced no obvious pathogenic variants in the coding regions of NFE2L2. Finally, we investigated the relationship between xenobiotic exposures and NRF2 function, through gene-environment interactions, between NFE2L2 SNPs and smoking or pesticide exposure. Our results demonstrated a significant interaction between rs2706110 and pesticide exposure (OR = 0.597 (0.393-0.900), P = 0.014). In addition, we were able to identify some age-at-onset modifying SNPs and replicate an 'early-onset' haplotype that contains a previously identified 'functional promoter' SNP (rs6721961). Our results suggest a role of NFE2L2 genetic variants in modifying PD susceptibility and onset. Our findings also support the utility of testing gene-environment interactions in genetic studies of PD.
We present a demonstration of delensing the observed cosmic microwave background (CMB) B-mode polarization anisotropy. This process of reducing the gravitational-lensing-generated B-mode component ...will become increasingly important for improving searches for the B modes produced by primordial gravitational waves. In this work, we delens B-mode maps constructed from multi-frequency SPTpol observations of a 90 deg2 patch of sky by subtracting a B-mode template constructed from two inputs: SPTpol E-mode maps and a lensing potential map estimated from the Herschel 500 m map of the cosmic infrared background. We find that our delensing procedure reduces the measured B-mode power spectrum by % in the multipole range this is shown to be consistent with expectations from simulations and to be robust against systematics. The null hypothesis of no delensing is rejected at . Furthermore, we build and use a suite of realistic simulations to study the general properties of the delensing process and find that the delensing efficiency achieved in this work is limited primarily by the noise in the lensing potential map. We demonstrate the importance of including realistic experimental non-idealities in the delensing forecasts used to inform instrument and survey-strategy planning of upcoming lower-noise experiments, such as CMB-S4.
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