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Background: The current investigation entails the characterization of seven degradation products (DPs) formed in different stress conditions of gilteritinib employing liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methodology: This study developed a stability-indicating reversed-phase high-performance liquid chromatographic (HPLC) method for precisely determining gilteritinib in the presence of its process-related impurities in bulk drug and formulation samples. To explore the stability profile of gilteritinib, it was exposed to forced degradation experiments conducted under various conditions, including acidic, basic, oxidative, photolytic, and thermal stress. These experiments revealed the degradation of gilteritinib under basic, acidic, and photolytic conditions, forming seven distinct DPs. Result: The chromatographic resolution of gilteritinib and its impurities along with DPs was effectively achieved using a Waters Symmetry C18 (250 mm × 4.6 mm, 5 μm) column using equal volumes of solvent A and B (pH 4.5 phosphate buffer and acetonitrile in 25:75 (v/v) as solvent A, acetonitrile and methanol in 75: 25 (v/v) as solvent B) pumped isocratically at 0.7 mL/min and 230 nm wavelength. The method produces an accurate fit calibration curve in 25-175 μg/mL for gilteritinib and LOQ (0.025 μg/mL) – 0.175 μg/mL for its impurities with acceptable precision, accuracy, and recovery. Conclusion: The efficacy of this method was validated through LC-MS/MS, which allowed for the verification of the chemical structures of newly generated degradation products of gilteritinib. Hence, this method is appropriate for the resolution and evaluation of process-related impurities of gilteritinib and can also be applied for evaluating stress degradation products.

Abstract In the Longwall mining method, the coal face is being supported with two-legged or four-legged shield supports which improve better roof control between the face and canopy tip. The development of load on the face increases with the face retreating rate or the increase of the overhung length behind the shield support and as a result, the coal face tends to yield/fail. The yield/failure zone in the face extends depending on intensity of developed load due to the depth of mining, panel size, height of excavation and geometry of the overhung. The broken coal from the yielded face may fall on the shearer, armoured flexible conveyor (AFC), shield supports or may hit the deployed manpower in the face and causes the face stoppage which in turn results in to the loss of the project. It is therefore, a study is conducted to understand the face yield/failure behaviour considering various geo-mining conditions based on input parameters such as main roof thickness, overhung length, and material type and setting load. This paper develops a unique statistical model to predict the yield/failure zone in the longwall face. For this purpose, a total of fifty-four (54) three-dimensional finite element models in ANSYS software are developed and analyzed considering Drucker-Prager failure criterion.

Abstract The implication of inflammation in the pathophysiology of several types of cancers has been under intense investigation. Conjugated fatty acids can modulate inflammation and present anticancer effects, promoting cancer cell death. In this paper, we evaluated the efficacy of new conjugated fatty acids isolated from marine Opisthopterus tardoore (Tapra fish) in human breast cancer cell lines MCF-7. Linoelaidic acid, a marine fish (O. tardoore) derived unsaturated fatty acids, showed effective anticancer activity against MCF-7. Cell viability (MTT) assay revealed a dose-dependent decline in cancer cell viability. It was noteworthy that 5 µM linoelaidic acid decreased the MCF-7 cell viability by 81.82%. Besides that, linoelaidic acid significantly (P

The 2:1 co-crystal of nadifloxacin [systematic name: 9-fluoro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid] with oxalic acid, C19H21FN2O4·0.5C2H2O4, was prepared by slow evaporation from a chloroform:acetone solvent system. Nadifloxacin belongs to the group of antibacterial drugs. The co-crystal is stabilized through an intramolecular O—H...O bond and intermolecular hydrogen bonds. It was studied by FT–IR spectroscopy, differential scanning calorimetry and X-ray diffraction. Hirshfeld surface analysis indicated that the major contribution to the packing is from O...H/H...O interactions.

Background: Familial hypercholesterolemia (FH) is common, but underdiagnosed, and few systematic early screening programs exist. Objective: To assess health outcomes among those with a recorded diagnosis of FH and potential cases of FH with no recorded diagnosis. Methods: Retrospective cohort study using the UK Clinical Practice Research Datalink. Records of adults were classified as diagnosed FH (FHCoded), or via accepted algorithms using LDL-C and clinical characteristics as potential FH (FHPotential) or unlikely FH (FHUnlikely) using the DLCN or EUROASPIRE criteria (but no record of FH). Outcomes assessed were premature cardiovascular (CV) events, premature deaths and life expectancy. Results: Among 1,729,046 individuals free from CV events, a record of FHCoded before the age of 40 was 0.3/1000 (IQR 0.3–0.4) and increased with age. Where LDL-C levels were available, 1.8/1000 (IQR 1.6–2.0) could be classified as FHPotential. LDL-C was higher for both FHCoded and FHPotential vs FHUnlikely (185.6 and 216.6 vs 116 mg/dL, respectively, p

Objective To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms.Design Prospective, open-label, multicentre, stratified, randomised clinical trial.Setting Five hospitals in UK and India, from September 2020 to May 2021.Participants Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset.Intervention Leflunomide 100 mg/day (3 days) followed by 10–20 mg/day (7 days) added to standard care.Primary outcomes The time to clinical improvement (TTCI) defined as two-point reduction on a clinical status scale or live discharge prior to 28 days; safety profile measured by the incidence of adverse events (AEs) within 28 days.Results Eligible patients (n=214; age 56.3±14.9 years; 33% female) were randomised to SOC+L (n=104) and SOC group (n=110), stratified according to their clinical risk profile. TTCI was 7 vs 8 days in SOC+L vs SOC group (HR 1.317; 95% CI 0.980 to 1.768; p=0.070). Incidence of serious AEs was similar between the groups and none was attributed to leflunomide. In sensitivity analyses, excluding 10 patients not fulfilling the inclusion criteria and 3 who withdrew consent before leflunomide treatment, TTCI was 7 vs 8 days (HR 1.416, 95% CI 1.041 to 1.935; p=0.028), indicating a trend in favour of the intervention group. All-cause mortality rate was similar between groups, 9/104 vs 10/110. Duration of oxygen dependence was shorter in the SOC+L group being a median 6 days (IQR 4–8) compared with 7 days (IQR 5–10) in SOC group (p=0.047).Conclusion Leflunomide, added to the SOC treatment for COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. It may shorten the time of oxygen dependence by 1 day and thereby improve TTCI/hospital discharge in moderately affected COVID-19 patients.Trial registration numbers EudraCT Number: 2020-002952-18, NCT05007678.

Abstract A fine-tuned combination of scaffolds, biomolecules, and mesenchymal stem cells (MSCs) is used in tissue engineering to restore the function of injured bone tissue and overcome the complications associated with its regeneration. For two decades, biomaterials have attracted much interest in mimicking the native extracellular matrix of bone tissue. To this aim, several approaches based on biomaterials combined with MSCs have been amply investigated. Recently, hydroxyapatite (HA) nanoparticles have been incorporated with polycaprolactone (PCL) matrix as a suitable substitute for bone tissue engineering applications. This review article aims at providing a brief overview on PCL/HA composite scaffold fabrication techniques such as sol–gel, rapid prototyping, electro-spinning, particulate leaching, thermally induced phase separation, and freeze-drying, as suitable approaches for tailoring morphological, mechanical, and biodegradability properties of the scaffolds for bone tissues. Among these methods, the 3D plotting method shows improvements in pore architecture (pore size of ≥600 µm and porosity of 92%), mechanical properties (higher than 18.38 MPa), biodegradability, and good bioactivity in bone tissue regeneration.

A novel compact-slotted four element multiple input multiple output (MIMO) planar monopole antenna is proposed for 5G mmWave N257/N258 and N262 band applications. The antenna, with dimensions of 12 mm × 11.6 mm × 0.508 mm (1.036λo ×1.001λo×0.043λo where λo is computed at lowest cutoff frequency), is fabricated on a Rogers RT/duroid 5880 (tm) substrate with a relative permittivity of 2.2 and a dielectric loss tangent of 0.0009. The suggested antenna consists of four U-shaped radiating elements (patches) on top of the dielectric material and a slotted ground on the bottom. The radiating elements are fed by a 50-ohm microstrip line feed. To improve the impedance performance of the MIMO antenna, a rectangular strip of 1.3 mm × 0.2 mm and a couple of rectangular slots are added to each radiating element. The first operating band at 27.1 GHz, ranging from 25.9 GHz to 27.8 GHz, is achieved by using slotted U-shaped radiating elements. The second operating band at 48.7 GHz, ranging from 47.1 GHz to 49.9 GHz, is obtained by etching hexagonal slots on the ground. The antenna design achieves an isolation of >27 dB through the orthogonal positioning of radiating elements and slots on the ground. The designed antenna operates at 27 GHz (N257/N258) and 48.7 GHz (N262) bands, exhibiting stable radiation patterns, a peak gain of >5.95 dBi, radiation efficiency of >90%, an envelope correlation coefficient of −6, a total active reflection coefficient of ≤−10 dB, channel capacity losses of

Introduction: Drugs are considered as double-edged weapons with the potential to cause benefit as well as harm. Recent studies reveal that adverse drug reactions (ADRs) imply a remarkable burden on the length of hospital stay, healthcare facilities, and sometimes they require additional investigations and drug therapies for the treatment of symptoms and diseases caused to the patient. So, further local studies are required to understand the scenario and to improve the safety of prescribing and monitoring drugs and improved patient adherence to medication. Objectives: To evaluate and assess the pattern of adverse drug reactions reported to the ADR Monitoring Centre, Rangaraya Medical College, Kakinada, India. Materials and Methods: The current study was a retrospective and an observational type of study carried out at the ADR Monitoring Centre of a tertiary care hospital. Total ADRs reported during the two years from June 2016 to June 2018 were included in the study. Each ADR was analyzed for demographic data, relationship to drugs as per causality assessment, and frequency of ADRs. Microsoft Excel 2019 and SPPS version 20 were used for data analysis. Results: The most common group of drugs showing ADRs were anti-retroviral therapy (ART) drugs, followed by anti-microbial agents. Most of the ADRs were probable and mild. Rash was the most frequently occurring ADR. Conclusion: The study of ADRs in a particular institute using demographic patterns will contribute to patient safety by sensitizing the clinicians in that particular institute.

BackgroundMore than 80% of individuals in low and middle-income countries (LMICs) are unvaccinated against coronavirus disease 2019 (COVID-19). In contrast, the greatest burden of cardiovascular disease is seen in LMIC populations. Hypertension (HTN), diabetes mellitus (DM), ischaemic heart disease (IHD) and myocardial injury have been variably associated with adverse COVID-19 outcomes. A systematic comparison of their impact on specific COVID-19 outcomes is lacking. We quantified the impact of DM, HTN, IHD and myocardial injury on six adverse COVID-19 outcomes: death, acute respiratory distress syndrome (ARDS), invasive mechanical ventilation (IMV), admission to intensive care (ITUadm), acute kidney injury (AKI) and severe COVID-19 disease (SCov), in an unvaccinated population.MethodologyWe included studies published between 1st December 2019 and 16th July 2020 with extractable data on patients ≥18 years of age with suspected or confirmed SARS-CoV-2 infection. Odds ratios (OR) for the association between DM, HTN, IHD and myocardial injury with each of six COVID-19 outcomes were measured.ResultsWe included 110 studies comprising 48,809 COVID-19 patients. Myocardial injury had the strongest association for all six adverse COVID-19 outcomes [death: OR 8.85 95% CI (8.08–9.68), ARDS: 5.70 (4.48–7.24), IMV: 3.42 (2.92–4.01), ITUadm: 4.85 (3.94–6.05), AKI: 10.49 (6.55–16.78), SCov: 5.10 (4.26–6.05)]. HTN and DM were also significantly associated with death, ARDS, ITUadm, AKI and SCov. There was substantial heterogeneity in the results, partly explained by differences in age, gender, geographical region and recruitment period.ConclusionCOVID-19 patients with myocardial injury are at substantially greater risk of death, severe disease and other adverse outcomes. Weaker, yet significant associations are present in patients with HTN, DM and IHD. Quantifying these associations is important for risk stratification, resource allocation and urgency in vaccinating these populations.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, registration no: CRD42020201435 and CRD42020201443.

Background: 3D cell culture is an appropriate method to develop engineered bone tissue, where different bioreactors have been designed to mitigate the challenges in 3D culture. Currently, we tailored a perfusion reactor to witness human mesenchymal stem cells (MSCs) proliferation and differentiation over polylactic acid-polyethylene glycol (PLA/PEG) composite scaffolds. Methods: The composite scaffolds with different weight ratios of PLA and PEG were prepared using solvent casting-particulate leaching technique. Human umbilcal card blood MSCs were cultured under dynamic and static conditions to elucidate the role of dynamic fluid flow in osteogenesis of MSCs. Results: The human MSCs distribution over the scaffolds was confirmed with fluorescent microscopy. Alkaline phosphatase (ALP), calcium mineralization, and collagen formation were found to be higher in PLA90 scaffolds than PLA100 and PLA75. PLA90 scaffolds with better cell adhesion/proliferartion were considered for bioreactor studies and they exhibited enhanced ALP, Ca+2 mineralization and collagen formation under dynamic perfusion than static culture. We further confirmed our observation by looking at expression levels of osteogenic marker (Runx2 and osteonectin) in differentiated MSCs subjected to perfusion culture compared to static culture. Conclusion: The results of the current investigation once again proves that dynamic perfusion cultures improve the osteogenic differentiation of MSCs over hybrid polymer scaffolds (PLA90) for effective bone regeneration. Keywords: 3D cell culture, Mesenchymal stem cells (MSCs), Fluid flow, Osteogenic differentiation

ROCK is associated with T cell movement in lymph nodes. Here the authors use an LPS lung damage model and two-photon imaging to show that CD8+ T cells in lung tissue engage in ROCK-dependent fast linear migration alternating with bursts of slower confined migration that together optimize contact with target cells.

The present study principally sought to investigate the effect of green tea extract (GTE) supplementation on hepatic mitochondrial DNA (mtDNA) damage in alcohol receiving rats. MtDNA was isolated from hepatic tissues of albino wistar rats after alcohol treatment with and without GTE supplementation. Entire displacement loop (D-loop) of mtDNA was screened by PCR-Sanger’s sequencing method. In addition, mtDNA deletions and antioxidant activity were measured in hepatic tissue of all rats. Results showed increased frequency of D-loop mutations in alcoholic rats (ALC). DNA mfold analysis predicted higher free energy for 15507C and 16116C alleles compared to their corresponding wild alleles which represents less stable secondary structures with negative impact on overall mtDNA function. Interestingly, D-loop mutations observed in ALC rats were successfully restored on GTE supplementation. MtDNA deletions were observed in ALC rats, but intact native mtDNA was found in ALC + GTE group suggesting alcohol induced oxidative damage of mtDNA and ameliorative effect of GTE. Furthermore, markedly decreased activities of glutathione peroxidise, superoxide dismutase, catalase and glutathione content were identified in ALC rats; however, GTE supplementation significantly (P

Corneal injuries are among the leading causes of blindness and vision impairment. Trauma, infectious keratitis, thermal and chemical (acids and alkali burn) injuries may lead to irreversible corneal scarring, neovascularization, conjunctivalization, and limbal stem cell deficiency. Bilateral blindness constitutes 12% of total global blindness and corneal transplantation remains a stand-alone treatment modality for the majority of end-stage corneal diseases. However, global shortage of donor corneas, the potential risk of graft rejection, and severe side effects arising from long-term use of immunosuppressive medications, demands alternative therapeutic approaches. Umbilical cord-derived mesenchymal stem cells can be isolated in large numbers using a relatively less invasive procedure. However, their role in injury induced corneal repair is largely unexplored. Here, we isolated, cultured and characterized mesenchymal stem cells from human umbilical cord, and studied the expression of mesenchymal (CD73, CD90, CD105, and CD34), ocular surface and epithelial (PAX6, WNT7A, and CK-8/18) lineage markers through immunofluorescence. The cultured human limbal and corneal epithelial cells were used as controls. Scratch assay was used to study the corneal epithelial repair potential of umbilical cord-derived mesenchymal stem cells, in vitro. The in vitro cultured umbilical cord-derived mesenchymal stem cells were plastic adherent, showed trilineage differentiation and expressed: mesenchymal markers CD90, CD105, CD73; epithelial marker CK-8/18, and ocular lineage developmental markers PAX6 and WNT-7A. Our findings suggest that umbilical cord-derived mesenchymal stem cells promote repair of the injured corneal epithelium by stimulating the proliferation of corneal epithelial cells, in vitro. They may serve as a potential non-ocular source of stem cells for treating injury induced bilateral corneal diseases.

We are interested in estimating the distribution of lifetimes, also called survival times, subject to a general censoring scheme called ``middle censoring'' (see Jammalamadaka and Mangalam (2003)). Both the Cox proportional hazards (Cox PH) and accelerated failure time (AFT) models are considered since each model has a baseline distribution function that is modified by the presence of covariates. The key contribution presented is the estimation of the effect of the covariate as well as the baseline distribution function. We conclude with an application to a contingent valuation study.

Middle censoring introduced by Jammalamadaka and Mangalam (2003), refers to data arising in situations where the exact lifetime becomes unobservable if it falls within a random censoring interval, otherwise it is observable. In the present paper we propose a semi-parametric regression model for such lifetime data, arising from an unknown population and subject to middle censoring. We provide an algorithm to find the nonparametric maximum likelihood estimator (NPMLE) for regression parameters and the survival function. The consistency of the estimators are established. We report simulation studies to assess the finite sample properties of the estimators. We then analyze a real life data on survival times for diabetic patients studied by Lee et al. (1988).

Line × Tester analysis involving three lines and four testers was carried out in ridge gourd [Luffa acutangula (Roxb.) L.]. Significant variation was noticed in the mean performance of the parents and hybrids for all the characters studied except for vine length and fruit girth. The results from GCA and SCA variance indicated the predominance of non-additive gene action for all the traits except fruit girth. Significant heterosis of 177.78% over standard check, Arka Sumeet for fruit weight per plant was expressed by the cross GARG-1 × CO-1. The best general combiners were GARG-1 and Pusa Nutan among the lines, and Jaipur long and CO-1 among testers. Best specific combining ability effects for fruit length and yield (t/ ha) were recorded by the crosses Pusa Nasdar × Arka Sumeet and GARG-1 × CO-1.

Recently closed loop pulsating heat pipes have been receiving much attention because of their potential applications in high heat flux micro-electronic systems. They work by self thermal driven oscillation without any mechanical parts. Though they are simple in structure, understanding of the heat transfer mechanism is highly complex having a strong thermo- hydro dynamic coupling governing their performance. In this paper, an experimental study on a closed loop PHP with a single turn has been conducted there by providing vital information regarding parameter dependence on its performance. The PHP is made of brass tube having an internal diameter of 2 mm and outer diameter of 3 mm. The parametric characterization has been done for the variation in internal diameter, fill ratio, working fluid and orientation of the device. The working fluids Acetone, Methanol, Ethanol and Propanol are considered for experimentation with volumetric filling ratios of 50%, 60%, 70% and 80%. Input heat power of 7 to 12 W is varied at the evaporator section. The CLPHP is also verified for its thermal performance at 00, 300 and 600 orientations. The transient and steady state experiments are conducted and operating temperatures are measured using K- type thermocouples. The results highlighted that the thermal performance of a PHPis strongly influenced by change in fill ratios, orientation and heat input. 80% fill ratio yields an effective heat transfer rate for a horizontal mode of operation. Appreciable fluid movement and better heat transfer rate are observed for the 300 orientation of PHP operation. Acetone exhibits better heat transport capability compared to other working fluids in all orientations.

We report the case of a 26-year-old lady gravida 5, with a revious Caesarean section who presented with 2 episodes of convulsions, shock and evidence of intrauterine foetal death. She was known to have epilepsy since childhood. Anticipating a scar dehiscence or rupture uterus she was posted for emergency laparotomy under spinal anaesthesia. Intra-operatively, 180o uterine torsion was evident. The uterus was untwisted and a lower segment caesarean section was performed to deliver the dead foetus. As the uterus remained flabby and did not retracted after correction of torsion, subtotal hysterectomy was done. She recovered well after surgery. The present case highlights uterine torsions, a rare but potentially dangerous and unexpected obstetric complication and reiterates the need for a timely intervention for better maternal and foetal outcome.

Carcinoma lower oesophagus metastasizing to thyroid occurs rarely. We report the case of a 56-year-old male who was referred for evaluation of dysphagia in whom such an occurrence has been documeneted. Clinically patient had palpable cervical lymphadenopathy. There was no thyroid swelling. Upper gastro-intestinal endoscopic biopsy revealed squamous cell carcinoma of lower third oesophagus. Fine needle aspiration cytology (FNAC) from the right cervical lymph node also revealed squamous cell carcinomatous deposits. Patient was then evaluated by integrated whole-body positron emission tomography-computed tomography using 18F fluorodeoxyglucose which revealed metabolic activity in thyroid gland. Ultrasound guided FNAC from thyroid shown metastatic squamous cell carcinomatous deposits which was further confirmed by imunocytochemistry. We present this case because of its exceedingly rare occurrence and poor prognosis.

A battery of toxicological studies was conducted in accordance with international guidelines to investigate the genotoxicity and repeated-dose oral toxicity in rats of synthetic curcumin (VEAMIN 99, >99% purity). There was no evidence of mutagenicity in a bacterial reverse mutation test, whereas an in vitro mammalian chromosomal aberration test was positive for induction of chromosomal aberrations which is in line with results reported for natural curcumin. There was no evidence of genotoxicity in an in vivo mammalian micronucleus test. Synthetic curcumin did not cause mortality or toxic effects in a 90-day repeated-dose oral toxicity study at daily doses of 250, 500, or 1000 mg/kg body weight (bw)/day (administered by gavage in a split dose). The no observed adverse effect level (NOAEL) determined from the 90-day study was 1000 mg/kg bw/day for both male and female Wistar rats.

Introduction: Acute pancreatitis is the sudden onset of reversible inflammation of pancreas in which pancreatic enzymes cause autodigestion of the gland. Acute pancreatitis varies from mild (mortality rate

Aims: The present study was investigated to optimize the production parameters using statistical method of the industrially important enzyme alkaline protease from newly isolated strain Pseudomonas putida from soil microorganisms. Methodology and results: Among 50 isolates of extensive screening two highly productive strains were selected. One among after biochemical characterization both laboratory level and by IMTECH Chandigarh was confirmed as P. putida. Submerged fermentation was carried out and statistical optimization methods Plackett and Burman and RSM were used to optimize the production parameters. Conclusion, significance and impact of study: Among the two selected strains out of 50 isolates, P. putida was identified as the one of the major protease producer. In this study eleven parameters were selected for the fractional factorial design (Plackett and Burman). Four significant parameters including time, carbon source, nitrogen source and salt showed significant impact on the alkaline protease production. During the study an increase in the alkaline protease activity from 4.659 U/mL to 7.396 U/mL was observed. Based on the above data more complex designs, such as Box Wilson design to study the impact of individual significant variable on the enzyme production as well as interactive effects among these significant variables were carried out. The interactive effect of the most influential parameters resulted in increase in enzyme activity from 7.246 up to 10.818 U/mL in 60 h. Analysis of variance showed the adequacy of the model and verification experiments confirmed its validity.

Background: To analyze the association between TLR-4 Asp299Gly and Thr399Ile gene polymorphisms and chronic periodontitis in a sample of south Indian population. Materials and Methods: Genomic DNA was obtained from peripheral blood of 60 patients with chronic periodontitis and 60 periodontally healthy subjects. TLR-4 Asp299Gly and Thr399Ile gene polymorphisms were genotyped by a polymerase chain reaction-restriction fragment length polymorphism method. The data were analyzed by a χ2-test and by relative risk estimation. Results: Thr399Ile alleles were found in 4% of chronic periodontitis patients and in 1% of periodontally healthy subjects. The prevalence of a Thr399Ile heterozygote was found to be 5% in the chronic periodontitis group and 1.67% in the periodontally healthy group, respectively. Homozygosity for TLR-4 Thr399Ile was seen in chronic periodontitis patients only, which was 1.67%. The TLR-4 Asp299Gly gene polymorphism was not detected in either chronic periodontitis or periodontally healthy groups. Conclusion: There is no significant association between TLR-4 Thr399Ile polymorphism and chronic periodontitis in a sample of south Indian population.

Ocean iron fertilization is an approach to increase CO2 sequestration. The Indo-German iron fertilization experiment LOHAFEX was carried out in the Southern Ocean surrounding Antarctica in 2009 to monitor changes in bacterial community structure following iron fertilization-induced phytoplankton bloom of the seawater from different depths. 16S rRNA gene libraries were constructed using metagenomic DNA from seawater prior to and after iron fertilization and the clones were sequenced for identification of the major bacterial groups present and for phylogenetic analyses. A total of 4439 clones of 16S rRNA genes from ten 16S rRNA gene libraries were sequenced. More than 97.35% of the sequences represented four bacterial lineages i.e. Alphaproteobacteria, Gammaproteobacteria, Bacteroidetes and Firmicutes and confirmed their role in scavenging of phytoplankton blooms induced following iron fertilization. The present study demonstrates the response of Firmicutes due to Iron fertilization which was not observed in previous southern ocean Iron fertilization studies. In addition, this study identifies three unique phylogenetic clusters LOHAFEX Cluster 1 (affiliated to Bacteroidetes), 2 and 3 (affiliated to Firmicutes) which were not detected in any of the earlier studies on iron fertilization. The relative abundance of these clusters in response to iron fertilization was different. The increase in abundance of LOHAFEX Cluster 2 and Papillibacter sp. another dominant Firmicutes may imply a role in phytoplankton degradation. Disappearance of LOHAFEX Cluster 3 and other bacterial genera after iron fertilization may imply conditions not conducive for their survival. It is hypothesised that heterotrophic bacterial abundance in the Southern Ocean would depend on their ability to utilise algal exudates, decaying algal biomass and other nutrients thus resulting in a dynamic bacterial succession of distinct genera.

Andrographolides, the diterpene lactones, are major bioactive phytochemicals which could be found in different parts of the medicinal herb Andrographis paniculata. A number of such compounds namely andrographolide (AG), neoandrographolide (NAG), and 14-deoxy-11,12-didehydroandrographolide (DDAG) have already attracted a great deal of attention due to their potential therapeutic effects in hard-to-treat diseases such as cancers and HIV. Recently, they have also been considered as substrates for the discovery of novel pharmaceutical compounds. Nevertheless, there is still a huge gap in knowledge on the genetic pattern of the biosynthesis of these bioactive compounds. Hence, the present study aimed to investigate the genetic mechanisms controlling the biosynthesis of these phytochemicals using a diallel analysis. The high performance liquid chromatography analysis of the three andrographolides in 210 F1 progenies confirmed that the biosynthesis of these andrographolides was considerably increased via intraspecific hybridization. The results revealed high, moderate and low heterosis for DDAG, AG and NAG, respectively. Furthermore, the preponderance of non-additive gene actions was affirmed in the enhancement of the three andrographolides contents. The consequence of this type of gene action was the occurrence of high broad-sense and low narrow-sense heritabilities for the above mentioned andrographolides. The prevalence of non-additive gene action suggests the suitability of heterosis breeding and hybrid seed production as a preferred option to produce new plant varieties with higher andrographolide contents using the wild accessions of A. paniculata. Moreover, from an evolutionary point of view, the occurrence of population bottlenecks in the Malaysian accessions of A. paniculata was unveiled by observing a low level of additive genetic variance (VA ) for all the andrographolides.

The yeast strain (Saccharomyces cerevisiae) MTCC 3157 was selected for combinatorial biosynthesis of plant sesquiterpene amorpha-4,11-diene. Our main objective was to overproduce amorpha 4-11-diene, which is a key precursor molecule of artemisinin (antimalarial drug) produced naturally in plant Artemisia annua through mevalonate pathway. Farnesyl diphosphate (FPP) is a common intermediate metabolite of a variety of compounds in the mevalonate pathway of yeast and leads to the production of ergosterols, dolichol and ubiquinone, and so forth. In our studies, FPP converted to amorphadiene (AD) by expressing heterologous amorphadiene synthase (ADS) in yeast. First, ERG9 (squalane synthase) promoter of yeast was replaced with repressible methionine (MET3) promoter by using bipartite gene fusion method. Further to overcome the loss of the intermediate FPP through competitive pathways in yeast, fusion protein technology was adopted and farnesyldiphosphate synthase (FPPS) of yeast has been coupled with amorphadiene synthase (ADS) of plant origin (Artemisia annua L.) where amorphadiene production was improved by 2-fold (11.2 mg/L) and 4-fold (25.02 mg/L) in yeast strains YCF-002 and YCF-005 compared with control strain YCF-AD (5.5 mg/L), respectively.

BackgroundAssociations between circulating markers of dysglycaemia and coronary heart disease (CHD) risk in people without diabetes have not been reliably characterised. We report new data from a prospective study and a systematic review to help quantify these associations.Methods and findingsFasting and post-load glucose levels were measured in 18,569 participants in the population-based Reykjavik study, yielding 4,664 incident CHD outcomes during 23.5 y of mean follow-up. In people with no known history of diabetes at the baseline survey, the hazard ratio (HR) for CHD, adjusted for several conventional risk factors, was 2.37 (95% CI 1.79-3.14) in individuals with fasting glucose > or = 7.0 mmol/l compared to those < 7 mmol/l. At fasting glucose values below 7 mmol/l, adjusted HRs were 0.95 (0.89-1.01) per 1 mmol/l higher fasting glucose and 1.03 (1.01-1.05) per 1 mmol/l higher post-load glucose. HRs for CHD risk were generally modest and nonsignificant across tenths of glucose values below 7 mmol/l. We did a meta-analysis of 26 additional relevant prospective studies identified in a systematic review of Western cohort studies that recorded fasting glucose, post-load glucose, or glycated haemoglobin (HbA(1c)) levels. In this combined analysis, in which participants with a self-reported history of diabetes and/or fasting blood glucose > or = 7 mmol/l at baseline were excluded, relative risks for CHD, adjusted for several conventional risk factors, were: 1.06 (1.00-1.12) per 1 mmol/l higher fasting glucose (23 cohorts, 10,808 cases, 255,171 participants); 1.05 (1.03-1.07) per 1 mmol/l higher post-load glucose (15 cohorts, 12,652 cases, 102,382 participants); and 1.20 (1.10-1.31) per 1% higher HbA(1c) (9 cohorts, 1639 cases, 49,099 participants).ConclusionsIn the Reykjavik Study and a meta-analysis of other Western prospective studies, fasting and post-load glucose levels were modestly associated with CHD risk in people without diabetes. The meta-analysis suggested a somewhat stronger association between HbA(1c) levels and CHD risk.