Background

The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.

Methods

We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time.

Findings

Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries.

Interpretation

Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

UV-vis spectroscopy and colorimetric models for detecting anthocyanin-metal complexes in plants: An overview of in vitro and in vivo techniques.

Deep eutectic solvent based advance microextraction method for determination of aluminum in water and food samples: Multivariate study.

Malaria, leishmaniasis, Chagas disease, and human African trypanosomiasis continue to cause considerable suffering and death in developing countries. Current treatment options for these parasitic protozoal diseases generally have severe side effects, may be ineffective or unavailable, and resistance is emerging. There is a constant need to discover new chemotherapeutic agents for these parasitic infections, and natural products continue to serve as a potential source. This review presents molecular docking studies of potential phytochemicals that target key protein targets in Leishmania spp., Trypanosoma spp., and Plasmodium spp.

The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.

Recently, the emergence and spread of pathogenic bacterial resistance to many antibiotics (multidrug-resistant strains) have been increasing throughout the world. This phenomenon is of great concern and there is a need to find alternative chemotherapeutic agents to combat these antibiotic-resistant microorganisms. Higher plants may serve as a resource for new antimicrobials to replace or augment current therapeutic options. In this work, we have carried out a molecular docking study of a total of 561 antibacterial phytochemicals listed in the Dictionary of Natural Products, including 77 alkaloids (17 indole alkaloids, 27 isoquinoline alkaloids, 4 steroidal alkaloids, and 28 miscellaneous alkaloids), 99 terpenoids (5 monoterpenoids, 31 sesquiterpenoids, 52 diterpenoids, and 11 triterpenoids), 309 polyphenolics (87 flavonoids, 25 chalcones, 41 isoflavonoids, 5 neoflavonoids, 12 pterocarpans, 10 chromones, 7 condensed tannins, 11 coumarins, 30 stilbenoids, 2 lignans, 5 phenylpropanoids, 13 xanthones, 5 hydrolyzable tannins, and 56 miscellaneous phenolics), 30 quinones, and 46 miscellaneous phytochemicals, with six bacterial protein targets (peptide deformylase, DNA gyrase/topoisomerase IV, UDP-galactose mutase, protein tyrosine phosphatase, cytochrome P450 CYP121, and NAD+-dependent DNA ligase). In addition, 35 known inhibitors were docked with their respective targets for comparison purposes. Prenylated polyphenolics showed the best docking profiles, while terpenoids had the poorest. The most susceptible protein targets were peptide deformylases and NAD+-dependent DNA ligases.

/pdf/the-search-for-herbal-antibiotics-an-in-silico-investigation-13no2mb3y7.pdf

The Search for Herbal Antibiotics: An In-Silico Investigation of Antibacterial Phytochemicals

A great number of sesquiterpenes are reported in the available literature as good antileishmanial leads. However, their mode of action at the molecular level has not been elucidated. The lack of molecular studies could be considered an impediment for studies seeking to improve sesquiterpene-based drug design. The present in silico study allows us to make important observations about the molecular details of the binding modes of a set of antileishmanial sesquiterpenes against four drug-enzyme targets [pteridine reductase-1 (PTR1), N-myristoyl transferase (NMT), cysteine synthase (CS), trypanothione synthetase (TryS)]. Through molecular docking it was found that two sesquiterpene coumarins are promising leads for the PTR1 and TryS inhibition purposes, and some xanthanolides also exhibited better affinity towards PTR1 and CS binding. In addition, the affinity values were clustered by Principal Component Analysis and drug-like properties were analyzed for the strongest-docking sesquiterpenes. The results are an excellent starting point for future studies of structural optimization of this kind of compounds.

/pdf/in-silico-analyses-of-sesquiterpene-related-compounds-on-43tndmpjz0.pdf

In-Silico Analyses of Sesquiterpene-Related Compounds on Selected Leishmania Enzyme-Based Targets

Exploitation of the complexation reaction of ortho-dihydroxylated anthocyanins with aluminum(III) for their quantitative spectrophotometric determination in edible sources.

Xanthones are secondary metabolites which have drawn considerable interest over the last decades due to their antimicrobial properties, among others A great number of this kind of compounds has been therefore reported, but there is a limited amount of studies on screening for biological activity Thus, as part of our research on antimicrobial agents of natural origin, a set of 272 xanthones were submitted to molecular docking (MD) calculations with a group of seven fungal and two viral enzymes The results indicated that prenylated xanthones are important hits for inhibition of the analyzed enzymes The MD scores were also analyzed by multivariate statistics Important structural details were found to be crucial for the inhibition of the tested enzymes by the xanthones In addition, the classification of active xanthones can be achieved by statistical analysis on molecular docking scores by an affinity-antifungal activity relationship approach The obtained results therefore are a suitable starting point for the development of antifungal and antiviral agents based on xanthones

Molecular docking and multivariate analysis of xanthones as antimicrobial and antiviral agents.

Fungal infections currently remain as a common problem in public health. Actually, drug discovery programs are oriented to the searching for lead structures. Virtual screening and molecular docking constitute great alternatives in order tofind hit compounds. Novel infection targets can also be defined and employed together with molecular docking tools in drug discovery programs. Thus, thirty-two natural compounds were docked within the active site of N-myristoyl transferase (NMT) as antifungal enzyme target. From tested compounds, alkaloids, flavonoids, xanthones, and quinones exhibited strongest mean interaction with NMT than terpenoids, coumarins and phenolics. Particularly, affinities for one aporphine alkaloid, a prenylated flavonoid and two xanthones resulted to be comparable with thatof previously reported synthetic inhibitor. Several hydrophobic and polar contacts were demonstrated by comparing different computational tools. The present results let to establish three possible lead structures to develop antifungal drugs although subsequent SAR analyses are still required.

/pdf/molecular-docking-study-of-naturallyoccurring-compounds-as-4dvdpoke9q.pdf

Molecular docking study of naturallyoccurring compounds as inhibitors of n-myristoyl transferase towards antifungal agents discovery

The calyxes of Hibiscus sabdariffa are used in traditional medicine around the world. However, quality assurance protocols and chemical variability have not been previously analyzed. In the present study, chemical characterization of a set of samples of H. sabdariffa calyxes commercialized in Colombia was accomplished with the aim to explore the chemical variability among them. Chemometrics-based analyses on the data obtained from the HPLC-UV-DAD-derived profiles were then performed. Thus, the pre-processed single-wavelength data were subjected to principal component analysis (PCA). The PCA-derived results evidenced different groups which were well-correlated to the corresponding total phenolic and total anthocyanin contents. Multi-wavelength chromatographic (HPLC-UV-DAD surfaces) data were additionally examined via parallel factor analysis (PARAFAC) as data reduction method and the obtained loadings were subsequently submitted to PCA and orthogonal partial least squares discriminant analysis (OPLS-DA). Results were thus consistent with those from single-wavelength data. PCA loadings were employed to determine those chemical components responsible for the data variance and OPLS-DA model, constructed from PARAFAC loadings, and indicated differentiation according total anthocyanin contents among samples. The present chemometric analysis therefore demonstrated to be an excellent tool for differentiation of H. sabdariffacalyxes according to their chemical composition.

Freddy A. Bernal

Papers

In-Silico Analyses of Sesquiterpene-Related Compounds on Selected Leishmania Enzyme-Based Targets

Exploitation of the complexation reaction of ortho-dihydroxylated anthocyanins with aluminum(III) for their quantitative spectrophotometric determination in edible sources.

Molecular docking and multivariate analysis of xanthones as antimicrobial and antiviral agents.

Molecular docking study of naturallyoccurring compounds as inhibitors of n-myristoyl transferase towards antifungal agents discovery

APPLICATION OF PARAFAC AND OPLS-DA ANALYSES ON HPLC FINGERPRINTS FOR THE CHARACTERIZATION OF Hibiscus sabdariffaCALYXES