A case of concomitant pulmonary tuberculosis and mucormycosis in an insulin-dependent diabetic patient

Conditions, where the patient's immune system is compromised are the main risk factor for mucormycosis. Approximately 23% of the world's population is estimated to have a latent Mycobacterium tuberculosis infection and more than 10 million new cases were estimated in 2017. Pulmonary mucormycosis and tuberculosis co-infections are very rare. We present the case of a 56-year-old insulin-dependent diabetic patient with a pulmonary mucormycosis and tuberculosis co-infection. While the patient did not suffer from ketoacidosis, she had poor glycemic control. A chest X-ray and a computed tomography showed nodular and cavitary lesions in both lungs. The patient was diagnosed through a biopsy of the bronchial mucosa and an RT-PCR for M. tuberculosis from bronchoalveolar lavage. The patient was treated with the recommended 4-drug regimen for TB (i.e. isoniazid, rifampin, pyrazinamide, and ethambutol); concurrently, amphotericin B deoxycholate was administered to treat the mucormycosis infection. Thirty days after initial hospital admission the patient underwent a lobectomy on the right lung. The case described here is only the sixth case reported in the literature of concomitant pulmonary tuberculosis and mucormycosis and the third case associated with a TB and mucormycosis co-infection involving an uncontrolled DM patient to survive

National, regional, and global estimates of anaemia by severity in women and children for 2000-19: a pooled analysis of population-representative data

BACKGROUND: Anaemia causes health and economic harms. The prevalence of anaemia in women aged 15-49 years, by pregnancy status, is indicator 2.2.3 of the UN Sustainable Development Goals, and the aim of halving the anaemia prevalence in women of reproductive age by 2030 is an extension of the 2025 global nutrition targets endorsed by the World Health Assembly (WHA). We aimed to estimate the prevalence of anaemia by severity for children aged 6-59 months, non-pregnant women aged 15-49 years, and pregnant women aged 15-49 years in 197 countries and territories and globally for the period 2000-19. METHODS: For this pooled analysis of population-representative data, we collated 489 data sources on haemoglobin distribution in children and women from 133 countries, including 4·5 million haemoglobin measurements. Our data sources comprised health examination, nutrition, and household surveys, accessed as anonymised individual records or as summary statistics such as mean haemoglobin and anaemia prevalence. We used a Bayesian hierarchical mixture model to estimate haemoglobin distributions in each population and country-year. This model allowed for coherent estimation of mean haemoglobin and prevalence of anaemia by severity. FINDINGS: Globally, in 2019, 40% (95% uncertainty interval [UI] 36-44) of children aged 6-59 months were anaemic, compared to 48% (45-51) in 2000. Globally, the prevalence of anaemia in non-pregnant women aged 15-49 years changed little between 2000 and 2019, from 31% (95% UI 28-34) to 30% (27-33), while in pregnant women aged 15-49 years it decreased from 41% (39-43) to 36% (34-39). In 2019, the prevalence of anaemia in children aged 6-59 months exceeded 70% in 11 countries and exceeded 50% in all women aged 15-49 years in ten countries. Globally in all populations and in most countries and regions, the prevalence of mild anaemia changed little, while moderate and severe anaemia declined in most populations and geographical locations, indicating a shift towards mild anaemia. INTERPRETATION: Globally, regionally, and in nearly all countries, progress on anaemia in women aged 15-49 years is insufficient to meet the WHA global nutrition target to halve anaemia prevalence by 2030, and the prevalence of anaemia in children also remains high. A better understanding of the context-specific causes of anaemia and quality implementation of effective multisectoral actions to address these causes are needed. FUNDING: USAID, US Centers for Disease Control and Prevention, and Bill & Melinda Gates Foundation

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Untargeted Metabolomics Used to Describe the Chemical Composition, Antioxidant and Antimicrobial Effects of Extracts from Pleurotus spp. Mycelium Grown in Different Culture Media

Pleurotus species isolated in vitro were studied to determine the effect of different media on their production of secondary metabolites, antimicrobial, and antioxidant activity. The different metabolites among Pleurotus samples covered a total of 58 pathways. Comparisons were made between the metabolic profiles of Pleurotus spp. mycelia grown in two substrates: Potato-dextroseagar-PDA, used as control (S1), and PDA enriched with 0.5 % of wheat straw (S2). The main finding was that the metabolic pathways are strongly influenced by the chemical composition of the growth substrate. The antibacterial effects were particularly evident against Escherichia coli, whereas Arthroderma curreyi (CCF 5207) and Trichophyton rubrum (CCF 4933) were the dermatophytes more sensitive to the mushroom extracts. The present study supports more in-depth investigations, aimed at evaluating the influence of growth substrate on Pleurotus spp. antimicrobial and antioxidant properties

Different rates of spontaneous mutation of chloroplastic and nuclear viroids as determined by high-fidelity ultra-deep sequencing

[EN] Mutation rates vary by orders of magnitude across biological systems, being higher for simpler genomes. The simplest known genomes correspond to viroids, subviral plant replicons constituted by circular non-coding RNAs of few hundred bases. Previous work has revealed an extremely high mutation rate for chrysanthemum chlorotic mottle viroid, a chloroplastreplicating viroid. However, whether this is a general feature of viroids remains unclear. Here, we have used high-fidelity ultra-deep sequencing to determine the mutation rate in a common host (eggplant) of two viroids, each representative of one family: the chloroplastic eggplant latent viroid (ELVd, Avsunviroidae) and the nuclear potato spindle tuber viroid (PSTVd, Pospiviroidae). This revealed higher mutation frequencies in ELVd than in PSTVd, as well as marked differences in the types of mutations produced. Rates of spontaneous mutation, quantified in vivo using the lethal mutation method, ranged from 1/1000 to 1/800 for ELVd and from 1/7000 to 1/3800 for PSTVd depending on sequencing run. These results suggest that extremely high mutability is a common feature of chloroplastic viroids, whereas the mutation rates of PSTVd and potentially other nuclear viroids appear significantly lower and closer to those of some RNA viruses.This work was supported by the European Research Council (erc.europa.eu; ERC-2011-StG-281191-VIRMUT to RS), the Spanish Ministerio de Economia y Competitividad (www.mineco.gob.es; BFU2013-41329 grant to RS, BFU2014-56812-P grant to RF, and a predoctoral fellowship to ALC), and the Spanish Junta de Comunidades de Castilla-La Mancha (www.castillalamancha.es;postdoctoral fellowship to CB). 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Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism

Objective: To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism. Methods: Hypervariable V3–V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n=33 and n=25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profles using bioinformatics in order to identify diferences in taxonomy and metabolic pathways. Results: We identifed a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifdobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_ UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabo‑ lism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed diferences in key bacterial enzymes involved in urate synthesis, degradation, and elimination. Conclusion: Our fndings revealed that taxonomic variations in the gut microbiome of gout patients with and with‑ out tophi might have a functional impact on urate metabolism. Keywords: Gout, Gut microbiota, Uric acid metabolis

NiftySim: A GPU-based nonlinear finite element package for simulation of soft tissue biomechanics

Purpose NiftySim, an open-source finite element toolkit, has been designed to allow incorporation of high-performance soft tissue simulation capabilities into biomedical applications. The toolkit provides the option of execution on fast graphics processing unit (GPU) hardware, numerous constitutive models and solid-element options, membrane and shell elements, and contact modelling facilities, in a simple to use library. Methods The toolkit is founded on the total Lagrangian explicit dynamics (TLEDs) algorithm, which has been shown to be efficient and accurate for simulation of soft tissues. The base code is written in C ++++ , and GPU execution is achieved using the nVidia CUDA framework. In most cases, interaction with the underlying solvers can be achieved through a single Simulator class, which may be embedded directly in third-party applications such as, surgical guidance systems. Advanced capabilities such as contact modelling and nonlinear constitutive models are also provided, as are more experimental technologies like reduced order modelling. A consistent description of the underlying solution algorithm, its implementation with a focus on GPU execution, and examples of the toolkit’s usage in biomedical applications are provided. Results Efficient mapping of the TLED algorithm to parallel hardware results in very high computational performance, far exceeding that available in commercial packages. Conclusion The NiftySim toolkit provides high-performance soft tissue simulation capabilities using GPU technology for biomechanical simulation research applications in medical image computing, surgical simulation, and surgical guidance applications

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Reaction rates and transport in neutron stars

Understanding signals from neutron stars requires knowledge about the transport inside the star. We review the transport properties and the underlying reaction rates of dense hadronic and quark matter in the crust and the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes, references updated, overview graphic added in the introduction, improvements in Sec IV.A.