SYNTHESIS AND CRYSTAL STRUCTURE ANALYSIS OF 3 - (4 - METHOXYBENZYL) - 2, 3 – DIHYDRO - 4H – CHROMAN – 4 - ONE

3-(4-methoxybenzyl)-2,3-dihydro-4H-chroman-4-one(C17H16 O3) was synthesized by refluxing 2'-Hydroxydihydrochalcone dissolved in ethanol with paraformaldehyde and 50% aqueous diethylamine. The compound is characterized by IR,1HNMR, MS and X-ray diffraction studies. The X-ray structure analysis indicates that the crystal suffers from the positional disorder over two positions, atomC1 and C9 with required site occupancies of 0.590 and 0.410 leading to a conformational difference between the major and minor components. After applying similarity restraints, the final reliability index is 0.0275 for 2209 unique reflections .The crystal packing is stabilized by inter molecular C-H…O, C-H…π and π …π interactions

Stability indicating HPLC determination of racecadotril in bulk drug and pharmaceutical dosage form

Se desarrolló y validó un nuevo método de cromatografía líquida de alto rendimiento, sencillo, rápido, reproducible e indicativo de la estabilidad, para el análisis del racecadotrilo en formulaciones farmacéuticas y como sustancia farmacológica al por mayor. La separación HPLC se realizó en una columna BDS -Hypersil C18 (250 mm X 4,6 mm, i.d. 5 μm de tamaño de partícula) utilizando una fase móvil formada por una mezcla de 20 mM de tampón fosfato (pH 3.5) y acetonitrilo en una proporción 40:60 y con una velocidad de fl ujo de 1 ml/min., con detección a 230 nm. Los datos del análisis de regresión lineal de las gráfi cas de calibración presentaron una buena relación lineal con un coefi ciente de correlación de 0,999 respecto al área de pico en el rango de concentración entre 5 μg/ml y 15 μg/ml. Se validó la precisión, exactitud, precisión, recuperación y robustez del método. Los límites de detección y determinación observados fueron de 50 y 100 ng/ml respectivamente. El racecadotrilo se sometió a hidrólisis ácida, hidrólisis alcalina y degradación oxidativa. El fármaco se degrada en condiciones ácidas, básicas y de oxidación. El análisis estadístico demuestra que el método es repetible, selectivo y preciso para la estimación de racecadotrilo. El método desarrollado y propuesto de HPLC se puede aplicar a la identifi cación y estimación del racecadotrilo en forma de dosifi cación oral sólida comercial y como sustancia farmacológica al por mayor.A new simple, rapid, reproducible and stability indicating high performance liquid chromatographic method for the analysis of racecadotril in bulk drugs and from pharmaceutical formulation was developed and validated. The HPLC separation was achieved on a BDS -Hypersil C18 column (250mm X 4.6mm, i.d. 5μm particle size) using a mobile phase consisting of a mixture of 20 mM phosphate buffer (pH 3.5) and acetonitrile in the ratio of (40:60) at a fl ow rate of 1 ml/min with detection at 230 nm. The linear regression analysis data for the calibration plots showed good linear relationship with the correlation coeffi cient of 0.999 with respect to peak area in the concentration range between 5 μg/ml and 15 μg/ml. The method was validated for precision, accuracy, recovery and robustness. The limit of detection and limit of quantitation were found to be 50 and 100 ng/ml respectively. Racecadotril was subjected to acid hydrolysis, alkali hydrolysis and oxidative degradation. The drug undergoes degradation under acidic, basic and oxidation conditions. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of racecadotril. The proposed developed HPLC method can be applied for identifi cation and estimation of racecadotril in bulk drugs and marketed oral solid dosage forms

Antidiabetic, hypolipidaemic and antioxidant activity of Dodonaea viscosa aerial parts in streptozotocin-induced diabetic rats

We evaluated the antidiabetic and antioxidant activity of Dodonaea viscosa in streptozotocin-induced diabetic rats. The water extract (DVW) and polar fraction of ethanol extract (DVE-4) in a single-dose one-day study showed dose-dependent reduction in glucose levels with maximum effect of 42.16% and 72.9% respectively at 6 h post drug treatment (p<0.001). DVE-4 was more active than DVW and glibenclamide. In a multi-dose fifteen-day study, lower doses of DVW (400 mg/kg) and DVE-4 (200 mg/kg) exhibited higher percentage reduction in glucose levels compared to glibenclamide treated group. Altered levels of lipids, TBARS, non-enzymatic and enzymatic antioxidants were restored by DVW (400 mg/kg) and DVE-4 (200 mg/kg) in diabetic rats. In vitro steady state and time resolved studies reveled that DVW and DVE-4 showed comparable antioxidant ability in steady state and kinetic studies suggesting its possible role in observed antidiabetic and hypolipidaemic activities.Keywords: Antidiabetic, Antioxidant enzymes, Dodonaea viscosa, Free radical scavenger, Hypolipidaemic, Streptozotoci

Differentiating Schizophrenia from Bipolar Illness on 18 F FDG PET CT Based on white Matter Metabolism; an under-Utilised Parameter

18F-FDG PET/CT positron emission tomography studies (FDG-PET) have shown similar cortico-limbic metabolic dysregulation in bipolar disorder and schizophrenia, with hypoactive prefrontal cortex coupled with hyperactive anterior limbic areas. However, it is not clear whether white matter metabolism connecting these regions is differently affected in the two disorders. Forty eight patients with schizophrenia mean age ± S.D] 31.6 ± 7.8 and 56 patients with bipolar disorder [mean age±S.D] 46.2 ± 8.9 underwent an 18F-FDG PET/CT scan. Normalized datasets the two groups of patients were compared on a voxel-by-voxel basis using a two-sample t statistic test as implemented in SPM8, and adding age as covariate. Group differences were assessed applying a threshold of p<0.0005. White matter metabolic rates significantly differed between schizophrenia and bipolar disorder, whereas no differences were shown for cortical activity. This is the first 18F-FDG PET/CT to our best knowledge, directly comparing subjects with schizophrenia to those with bipolar disorder. It reports decreased activity in the center of large fronto-temporal and cerebellar white matter tracts in patients with schizophrenia in respect to those with bipolar disorder. This feature may characterize and differentiate the regional brain metabolism of the two illnesses

18F-FDG PET/CT Evaluation of Regional Cerebral Metabolic Activities in Childhood Onset Schizophrenia

Introduction: Functional neuro-imaging with FDG PET CT in schizophrenic patients have reported certain patterns of increased or decreased metabolism in specific areas of the brain. Frontal lobe is one of the cortical areas consistently associated with schizophrenia and the activity levels have been reported to vary with the symptomatology at presentation. Predominantly positive symptoms cause and underlying hyperfrontality and negative symptoms are associated with hypofrontality. This study aims to assess the imaging patterns in unmedicated pediatric patients with a diagnosis of schizophrenia and predominantly positive symptoms.Patients and methods: 48 pediatric patients with a diagnosis of schizophrenia (all unmedicated, 38 never medicated) and 10 healthy age-matched controls were evaluated with FDG PET CT. The patients met ICD-10 and DSM-IV criteria for schizophrenia and all reported psychotic, “positive†symptoms when tested.Results: Children with schizophrenia and positive symptoms had a pattern of diffuse hyper-metabolism involving the bilateral frontal cortices and could be demonstrated on quantification by region to occipital ratio comparison . Associated statistically significant differences were also found when comparing ratios of occipital to thalamic, striatal and temporal cortex in these patients when compared to controls.Conclusion: Diffuse frontal hypermetabolism or hyperfrontality is observed in children with schizophrenia when there is a predominance of positive symptoms. There could be a possible disruption of cortico-striato-thalamic feedback loops causing hyperfrontality as seen in in experimentally induced models of psychosis

The Role of Radioactivities in Astrophysics

I present both a history of radioactivity in astrophysics and an introduction to the major applications of radioactive abundances to astronomy

Current status of the multinational Arabidopsis community

The multinational Arabidopsis research community is highly collaborative and over the past thirty years these activities have been documented by the Multinational Arabidopsis Steering Committee (MASC). Here, we (a) highlight recent research advances made with the reference plant Arabidopsis thaliana; (b) provide summaries from recent reports submitted by MASC subcommittees, projects and resources associated with MASC and from MASC country representatives; and (c) initiate a call for ideas and foci for the “fourth decadal roadmap,” which will advise and coordinate the global activities of the Arabidopsis research community

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

BACKGROUND: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. METHODS: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. FINDINGS: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. INTERPRETATION: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66–2•79) in 2000 to 2•31 (2•17–2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5–137•8) in 2000 to a peak of 139•6 million (133•0–146•9) in 2016. Global livebirths then declined to 135•3 million (127•2–144•1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2•1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27•1% (95% UI 26•4–27•8) of global livebirths. Global life expectancy at birth increased from 67•2 years (95% UI 66•8–67•6) in 2000 to 73•5 years (72•8–74•3) in 2019. The total number of deaths increased from 50•7 million (49•5–51•9) in 2000 to 56•5 million (53•7–59•2) in 2019. Under-5 deaths declined from 9•6 million (9•1–10•3) in 2000 to 5•0 million (4•3–6•0) in 2019. Global population increased by 25•7%, from 6•2 billion (6•0–6•3) in 2000 to 7•7 billion (7•5–8•0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58•6 years (56•1–60•8) in 2000 to 63•5 years (60•8–66•1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens