The utility of red cell distribution width to predict mortality of septic patients in a tertiary hospital of Nepal.

BACKGROUND: Sepsis is a common problem encountered in the emergency room which needs to be intervened early. Predicting prognosis is always a difficult task in busy emergency rooms using present scores, which has several variables to calculate. Red cell distribution width (RDW) is an easy, cheap, and efficacious score to predict the severity and mortality of patients with sepsis. METHODS: This prospective analytical study was conducted in the emergency room of Tribhuvan University Teaching Hospital among the patients age ≥ 16 years and with a clinical diagnosis of sepsis using qSOFA score. 148 patients were analyzed in the study by using a non-probability purposive sampling method. RESULTS: RDW has fair efficacy to predict the mortality in sepsis (Area under the Curve of 0.734; 95% C. I = 0.649-0.818; p-value = 0.000) as APACHE II (AUC of 0.728; 95% C. I = 0.637 to 0.819; p-value = 0.000) or SOFA (AUC of 0.680, 95% C. I = 0.591-0.770; p-value = 0.001). Youden Index was maximum (37%) at RDW value 14.75, which has a sensitivity of 83% (positive likelihood ratio = 1.81) and specificity of 54% (negative likelihood ratio = 0.32). Out of 44 patients with septic shock 16 died (36.4%) and among 104 patients without septic shock, 24 died (22.9%) which had the odds ratio of 0.713 (p = 0.555, 95% C. I = 0.231-2.194). Overall mortality was 27.02% (n = 40). RDW group analysis showed no mortality in RDW < 13.1 group, 3.6% mortality in 13.1 to 14 RDW group, 22.0% mortality in 14 to > 15.6 RDW group and 45.9% mortality in > 15.6 RDW group. Significant mortality difference was seen in 14 to > 15.6 and > 15.6 RDW subgroups with a p-value of 0.003 and 0.008 respectively. CONCLUSION: Area under the curve value for RDW is fair enough to predict the mortality of patients with sepsis in the emergency room. It can be integrated with other severity scores (APACHE II or SOFA score) for better prediction of prognosis of septic patients.

The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research.

Covering: up to 2018With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.

Correction: The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research.

Correction for 'The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research' by James B. McAlpine et al., Nat. Prod. Rep., 2018, DOI: .

Myrmenaphthol A, Isolated from a Hawaiian Sponge of the Genus Myrmekioderma.

Four compounds (1-4) were isolated from a Hawaiian sponge of the genus Myrmekioderma. Myrmenaphthol A (1) incorporates two unusual elements into an oxidized steroidal core: a naphthyl AB-ring system and a hydroxy group at C-2. A comparison of the experimental and predicted electronic circular dichroism (ECD) spectra of 1 assigned an S configuration to the lone stereocenter (ΔESI = 0.75; similarity factor 0.8137). Known compounds, cinanthrenol A (2), 3,4-dihydroxypregna-5,17-diene-10,2-carbolactone (3), and 3,4-dihydroxypregna-5,20-diene-10,2-carbolactone (4), were also isolated. Despite literature reports of competitive inhibition at nanomolar levels for 2, neither 2 nor the structurally related 1 showed any activity against estrogen receptors at the concentrations tested.

Cytotoxic Sesquiterpenoid Quinones and Quinols, and an 11-Membered Heterocycle, Kauamide, from the Hawaiian Marine Sponge Dactylospongia elegans.

Several known sesquiterpenoid quinones and quinols (1-9), and kauamide (10), a new polyketide-peptide containing an 11-membered heterocycle, were isolated from the extracts of the Hawaiian marine sponge Dactylospongia elegans. The planar structure of 10 was determined from spectroscopic analyses, and its relative and absolute configurations were established from density functional theory (DFT) calculations of the GIAO NMR shielding tensors, and advanced Marfey's analysis of the N-MeLeu residue, respectively. Compounds 1 and 3 showed moderate inhibition of ß-secretase 1 (BACE1), whereas 1-9 exhibited moderate to potent inhibition of growth of human glioma (U251) cells. Compounds 1-2 and 4-7 were also active against human pancreatic carcinoma (Panc-1) cells.

Catalyst-Free Plasma Enhanced Growth of Graphene from Sustainable Sources.

Details of a fast and sustainable bottom-up process to grow large area high quality graphene films without the aid of any catalyst are reported in this paper. We used Melaleuca alternifolia, a volatile natural extract from tea tree plant as the precursor. The as-fabricated graphene films yielded a stable contact angle of 135°, indicating their potential application in very high hydrophobic coatings. The electronic devices formed by sandwiching pentacene between graphene and aluminum films demonstrated memristive behavior, and hence, these graphene films could find use in nonvolatile memory devices also.

Evaluating the impacts of landscape positions and nitrogen fertilizer rates on dissolved organic carbon on switchgrass land seeded on marginally yielding cropland.

Dissolved organic carbon (DOC) through leaching into the soils is another mechanism of net C loss. It plays an important role in impacting the environment and impacted by soil and crop management practices. However, little is known about the impacts of landscape positions and nitrogen (N) fertilizer rates on DOC leaching in switchgrass (Panicum virgatum L.). This experimental design included three N fertilizer rates [0 (low); 56 (medium); 112 (high) kg N ha(-1)] and three landscape positions (shoulder, backslope and footslope). Daily average DOC contents at backslope were significantly lower than that at shoulder and footslope. The DOC contents from the plots that received medium N rate were also significantly lower than the plots that received low N rates. The interactions of landscape and N rates on DOC contents were different in every year from 2009 to 2014, however, no significant consistent trend of DOC contents was observed over time. Annual average DOC contents from the plots managed with low N rate were higher than those with high N rate. These contents at the footslope were higher than that at the shoulder position. Data show that there is a moderate positive relationship between the total average DOC contents and the total average switchgrass biomass yields. Overall, the DOC contents from leachate in the switchgrass land were significantly influenced by landscape positions and N rates. The N fertilization reduced DOC leaching contents in switchgrass field. The switchgrass could retain soil and environment sustainability to some extent. These findings will assist in understanding the mechanism of changes in DOC contents with various parameters in the natural environment and crop management systems. However, use of long-term data might help to better assess the effects of above factors on DOC leaching contents and loss in the switchgrass field in the future.

Invasion speeds with active dispersers in highly variable landscapes: Multiple scales, homogenization, and the migration of trees.

The distribution of many tree species is strongly determined by the behavior and range of vertebrate dispersers, particularly birds. Many models for seed dispersal exist, and are built around the assumption that seeds undergo a random walk while they are being carried by vertebrates, either in the digestive tract or during the process of seed storage (caching). We use a PDF of seed handling (caching and digesting) times to model non-constant seed settling during dispersal, and model the random component of seed movement using ecological diffusion, in which animals make movement choices based purely on local habitat type instead of population gradients. Spatial variability in habitat directly affects the movement of dispersers and leads to anisotropic dispersal kernels. For birds, which can easily move many kilometers, habitat changes on the scale of tens of meters can viewed as rapidly varying. We introduce multiple scales and apply the method of homogenization to determine leading order solutions for the seed digestion kernel (SDK). Using an integrodifference equation (IDE) model for adult trees, we investigate the rate of forest migration. The existing theory for predicting spread rates in IDE does not apply when dispersal kernels are anisotropic. However, the homogenized SDK is isotropic on large scales and depends only on harmonically averaged motilities and modal rates of digestion. We show that speeds calculated using the harmonic average motility accurately predict rates of invasion for the spatially variable system.

The relationship of serum amylase levels in acute organophosphorus poisoning with its clinical severity and outcome: a cross-sectional study.

There are limited literatures studying the pancreatic involvement in organophosphate (OP) poisoning using biochemical means. This study focused on assessing the type of OP poisoning and determining the association of serum amylase levels with the patient's presentation and outcome. Materials and methods: A cross-sectional study was carried out in the Maharajgunj Medical Campus, Tribhuwan University Teaching Hospital, Kathmandu, Nepal, after ethical approval [Ref: IRB/308 (6-11-E)]. We collected data from 172 participants with OP poisoning over the period of 2 years using nonprobability purposive sampling method. All patients with age group 16-75 years having a history of OP poisoning within the previous 24 h with clinical features and physical evidence of poisoning were included in the study. Those participants with indications of exposure to an entirely different poisons, poisoning with multiple poisons, OP poisoning along with alcohol, chronic alcoholics, comorbid conditions, taking drugs that could affect serum amylase levels (azathioprine, thiazides, furosemide, etc.), and/or treated in other hospitals after poisoning were excluded from the study. Appropriate statistical calculations were made using the statistical package for social sciences (SPSS), version 21. The P-value of less than 0.05 was considered statistically significant. Results: Metacid (53.5%, 92) was the most common OP poison. There were significantly higher mean values of serum amylase levels either within 12 h of exposure (468.60 vs. 135.4 IU/ml, P<0.001) or after 12 h of exposure (152.0 vs. 58.9 IU/ml, P<0.001) in dead participants than alive ones. The participants with initial and after 12 h of exposure-serum amylase level 100 or more IU/ml had more than two-fold and 18-fold higher odds of severe/life-threatening severity (odds ratio=2.40, 95% CI: 1.28-4.52, P=0.007 and odds ratio=18.67, 95% CI: 8.02-43.47, P<0.001) respectively than those with less than 100 IU/ml. Conclusions: The clinical severity of OP poisoning is directly related to serum amylase levels. Importantly, higher mean values of serum amylase levels were depicted in those participants with OP poisoning culminating to death. Thus, serum amylase level could be one of the easy measurable prognostic marker of OP poisonings.

Acidic Cannabinoids Suppress Proinflammatory Cytokine Release by Blocking Store-operated Calcium Entry.

Cannabis sativa has long been known to affect numerous biological activities. Although plant extracts, purified cannabinoids, or synthetic cannabinoid analogs have shown therapeutic potential in pain, inflammation, seizure disorders, appetite stimulation, muscle spasticity, and treatment of nausea/vomiting, the underlying mechanisms of action remain ill-defined. In this study we provide the first comprehensive overview of the effects of whole-plant Cannabis extracts and various pure cannabinoids on store-operated calcium (Ca2+) entry (SOCE) in several different immune cell lines. Store-operated Ca2+ entry is one of the most significant Ca2+ influx mechanisms in immune cells, and it is critical for the activation of T lymphocytes, leading to the release of proinflammatory cytokines and mediating inflammation and T cell proliferation, key mechanisms for maintaining chronic pain. While the two major cannabinoids cannabidiol and trans-Δ9-tetrahydrocannabinol were largely ineffective in inhibiting SOCE, we report for the first time that several minor cannabinoids, mainly the carboxylic acid derivatives and particularly cannabigerolic acid, demonstrated high potency against SOCE by blocking calcium release-activated calcium currents. Moreover, we show that this inhibition of SOCE resulted in a decrease of nuclear factor of activated T-cells activation and Interleukin 2 production in human T lymphocytes. Taken together, these results indicate that cannabinoid-mediated inhibition of a proinflammatory target such as SOCE may at least partially explain the anti-inflammatory and analgesic effects of Cannabis.

Enantioselective hydroformylation of N-vinyl carboxamides, allyl carbamates, and allyl ethers using chiral diazaphospholane ligands.

Rhodium complexes of diazaphospholane ligands catalyze the asymmetric hydroformylation of N-vinyl carboxamides, allyl ethers, and allyl carbamates; products include 1,2- and 1,3-aminoaldehydes and 1,3-alkoxyaldehydes. Using glass pressure bottles, short reaction times (generally less than 6 h), and low catalyst loading (commonly 0.5 mol %), 20 substrates are successfully converted to chiral aldehydes with useful regioselectivity and high enantioselectivity (up to 99% ee). Chiral Roche aldehyde is obtained with 97% ee from the hydroformylation of allyl silyl ethers. Commonly difficult substrates such as 1,1- and 1,2-disubstituted alkenes undergo effective hydroformylation with 89-97% ee and complete conversion for six examples. Palladium-catalyzed aerobic oxidative amination of allyl benzyl ether followed by enantioselective hydroformylation yields the ß(3)-aminoaldehyde with 74% ee.

Characterization of Leptazolines A-D, Polar Oxazolines from the Cyanobacterium Leptolyngbya sp., Reveals a Glitch with the "Willoughby-Hoye" Scripts for Calculating NMR Chemical Shifts.

The bioactivity-guided examination of a Leptolyngbya sp. led to the isolation of leptazolines A-D (1-4), from the culture media, along with two degradation products (5 and 6). Density functional theory nuclear magnetic resonance calculations established the relative configurations of 1 and 2 and revealed that the calculated shifts depended on the operating system when using the "Willoughby-Hoye" Python scripts to streamline the processing of the output files, a previously unrecognized flaw that could lead to incorrect conclusions.

The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discovery.

Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compound characterization and identification are being hampered by the lack of a comprehensive database of known compounds against which to compare experimental data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no standard format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have associated structure files (e.g., MOL, InChI, or SMILES), instead containing images of structures. This makes extraction and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24 594 compounds and contains referenced data for structure, compound names, source organisms, isolation references, total syntheses, and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and physical properties. The Web site also provides mechanisms for visualizing natural products chemical space and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Minimum Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Molecular Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms and is the first comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries.

Areca nut extracts mobilize calcium and release pro-inflammatory cytokines from various immune cells.

Betel nut consumption has significant implications for the public health globally, as the wide-spread habit of Areca chewing throughout Asia and the Pacific is associated with a high prevalence of oral carcinoma and other diseases. Despite a clear causal association of betel nut chewing and oral mucosal diseases, the biological mechanisms that link Areca nut-contained molecules, inflammation and cancer remain underexplored. In this study we show that the whole Areca nut extract (ANE) is capable of mobilizing Ca2+ in various immune cell lines. Interestingly, none of the four major alkaloids or a range of other known constituents of Areca nut were able to induce such Ca2+ signals, suggesting that the active components might represent novel or so far unappreciated chemical structures. The separation of ANE into aqueous and organic fractions has further revealed that the calcium-mobilizing molecules are exclusively present in the aqueous extract. In addition, we found that these calcium signals are associated with the activation of several immune cell lines as shown by the release of pro-inflammatory cytokines and increased cell proliferation. These results indicate that calcium-mobilizing molecules present in the aqueous fraction of the Areca nut may critically contribute to the inflammatory disorders affecting betel nut chewers.

Observation of a low temperature n-p transition in individual titania nanotubes.

Manipulating the transport properties of titania nanotubes (NTs) is paramount in guaranteeing the material's successful implementation in various solid state applications. Here we present the unique semiconducting properties of individual titania NTs as revealed from thermoelectric and structural studies performed on the same individual NTs. The NTs were in the anatase phase fabricated by anodic oxidation and doped with intrinsic defects created by reducing the lattice thermally. Despite their polycrystalline nature and nanoscale walls, the doped NTs were found to be 4-5 orders of magnitude more electrically conducting than TiO2 nanowires and thin films, with values approaching the bulk single crystal conductivity. The reason for the high conductivity was found to be the high carrier concentration on the order of 1022 cm-3, which counteracted the low mobility values ∼0.006 cm2 V-1 s-1. Furthermore, this high level of carrier concentration transitioned the NTs to a degenerate state, which is the first such example in thermally doped titania NTs. More importantly, our study showed the creation of acceptor states along with donor states in individual nanotubes upon lattice reduction. These acceptor levels were found to be active at low temperatures when donor states were not ionized, shifting the Fermi level (Ef) from the conduction band to the valence band.

Exfoliation of a non-van der Waals material from iron ore hematite.

With the advent of graphene, the most studied of all two-dimensional materials, many inorganic analogues have been synthesized and are being exploited for novel applications. Several approaches have been used to obtain large-grain, high-quality materials. Naturally occurring ores, for example, are the best precursors for obtaining highly ordered and large-grain atomic layers by exfoliation. Here, we demonstrate a new two-dimensional material 'hematene' obtained from natural iron ore hematite (α-Fe2O3), which is isolated by means of liquid exfoliation. The two-dimensional morphology of hematene is confirmed by transmission electron microscopy. Magnetic measurements together with density functional theory calculations confirm the ferromagnetic order in hematene while its parent form exhibits antiferromagnetic order. When loaded on titania nanotube arrays, hematene exhibits enhanced visible light photocatalytic activity. Our study indicates that photogenerated electrons can be transferred from hematene to titania despite a band alignment unfavourable for charge transfer.