Nontuberculous Mycobacterial Disease in Children – Epidemiology,Diagnosis & Management at a Tertiary Center

Background

There are limited data on the epidemiology, diagnosis and optimal management of nontuberculous mycobacterial (NTM) disease in children.

Methods

Retrospective cohort study of NTM cases over a 10-year-period at a tertiary referral hospital in Australia.

Results

A total of 140 children with NTM disease, including 107 with lymphadenitis and 25 with skin and soft tissue infections (SSTIs), were identified. The estimated incidence of NTM disease was 0.6–1.6 cases / 100,000 children / year; no increasing trend was observed over the study period. Temporal analyses revealed a seasonal incidence cycle around 12 months, with peaks in late winter/spring and troughs in autumn. Mycobacterium-avium-complex accounted for most cases (77.8%), followed by Mycobacterium ulcerans (14.4%) and Mycobacterium marinum (3.3%). Polymerase chain reaction testing had higher sensitivity than culture and microscopy for acid-fast bacilli (92.0%, 67.2% and 35.7%, respectively). The majority of lymphadenitis cases underwent surgical excision (97.2%); multiple recurrences in this group were less common in cases treated with clarithromycin and rifampicin compared with clarithromycin alone or no anti-mycobacterial drugs (0% versus 7.1%; OR:0.73). SSTI recurrences were also less common in cases treated with two anti-mycobacterial drugs compared with one or none (10.5% versus 33.3%; OR:0.23).

Conclusions

There was seasonal variation in the incidence of NTM disease, analogous to recently published observations in tuberculosis, which have been linked to seasonal variation in vitamin D. Our finding that anti-mycobacterial combination therapy was associated with a reduced risk of recurrences in patients with NTM lymphadenitis or SSTI requires further confirmation in prospective trials.     

Retinoic Acid Specifically Enhances Embryonic Stem Cell Metastate Marked by Zscan4

Pluripotency confers Embryonic Stem Cells (ESCs) the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. Although the majority of ESCs divide without losing pluripotency, it has become evident that ESCs culture consists of multiple cell populations with different degrees of potency that are spontaneously induced in regular ESC culture conditions. Zscan4, a key pluripotency factor, marks ESC subpopulation that is referred to as high-level of pluripotency metastate. Here, we report that in ESC cultures treated with retinoic acid (RA), Zscan4 ESCs metastate is strongly enhanced. In particular, we found that induction of Zscan4 metastate is mediated via RA receptors (RAR-alpha, RAR-beta, and RAR-gamma), and it is dependent on phosphoinositide-3-kinase (PI3K) signaling. Remarkably, Zscan4 metastate induced by RA lacks canonical pluripotency genes Oct3/4 and Nanog but retained both self-renewal and pluripotency capabilities. Finally we demonstrated that the conditional ablation of Zscan4 subpopulation is dispensable for both endoderm and mesoderm but is required for ectoderm lineage. In conclusion, our research provides new insights about the role of RA signaling during ESCs high pluripotency metastate fluctuation.     

Protective Role of False Tendon in Subjects with Left Bundle Branch Block: A Virtual Population Study

False tendons (FTs) are fibrous or fibromuscular bands that can be found in both the normal and abnormal human heart in various anatomical forms depending on their attachment points, tissue types, and geometrical properties. While FTs are widely considered to affect the function of the heart, their specific roles remain largely unclear and unexplored. In this paper, we present an in silico study of the ventricular activation time of the human heart in the presence of FTs. This study presents the first computational model of the human heart that includes a FT, Purkinje network, and papillary muscles. Based on this model, we perform simulations to investigate the effect of different types of FTs on hearts with the electrical conduction abnormality of a left bundle branch block (LBBB). We employ a virtual population of 70 human hearts derived from a statistical atlas, and run a total of 560 simulations to assess ventricular activation time with different FT configurations. The obtained results indicate that, in the presence of a LBBB, the FT reduces the total activation time that is abnormally augmented due to a branch block, to such an extent that surgical implant of cardiac resynchronisation devices might not be recommended by international guidelines. Specifically, the simulation results show that FTs reduce the QRS duration at least 10 ms in 80% of hearts, and up to 45 ms for FTs connecting to the ventricular free wall, suggesting a significant reduction of cardiovascular mortality risk. In further simulation studies we show the reduction in the QRS duration is more sensitive to the shape of the heart then the size of the heart or the exact location of the FT. Finally, the model suggests that FTs may contribute to reducing the activation time difference between the left and right ventricles from 12 ms to 4 ms. We conclude that FTs may provide an alternative conduction pathway that compensates for the propagation delay caused by the LBBB. Further investigation is needed to quantify the clinical impact of FTs on cardiovascular mortality risk.     

Computational evaluation of load carriage effects on gait balance stability

Evaluating the effects of load carriage on gait balance stability is important in various applications. However, their quantification has not been rigorously addressed in the current literature, partially due to the lack of relevant computational indices. The novel Dynamic Gait Measure (DGM) characterizes gait balance stability by quantifying the relative effects of inertia in terms of zero-moment point, ground projection of center of mass, and time-varying foot support region. In this study, the DGM is formulated in terms of the gait parameters that explicitly reflect the gait strategy of a given walking pattern and is used for computational evaluation of the distinct balance stability of loaded walking. The observed gait adaptations caused by load carriage (decreased single support duration, inertia effects, and step length) result in decreased DGM values (p < 0.0001), which indicate that loaded walking motions are more statically stable compared with the unloaded normal walking. Comparison of the DGM with other common gait stability indices (the maximum Floquet multiplier and the margin of stability) validates the unique characterization capability of the DGM, which is consistently informative of the presence of the added load.     

Assessing lignocellulosic biomass production from crop residues in the European Union: Modelling,analysis of the current scenario and drivers of interannual variability

This study assesses crop residues in the EU from major crops using empirical models to predict crop residues from yield statistics; furthermore it analyses the inter‐annual variability of those estimates over the period 1998‐2015, identifying its main drivers across Europe. The models were constructed based on an exhaustive collection of experimental data from scientific papers for the crops: wheat, barley, rye, oats, triticale, rice, maize, sorghum, rapeseed, sunflower, soybean, potato and sugarbeet. We discuss the assumptions on the relationship between yield and the harvest index, adopted by previous studies, to interpret the experimental data, quantify the uncertainties of these models, and establish the premises to implement them at regional scale –i.e., NUTS level 3– within the EU. To cope this, we created a consolidated sub‐national statistical data along with an algorithm able to aggregate (figures are provided at country level) and disaggregate (production at 25 km grid is provided assupplementary material) estimates. The total lignocellulosic biomass production in the EU28 over the review period, according to our models, is 419 Mt, from which wheat is the major contributor (155 Mt). Our results show that maize and rapeseed are the two crops with the highest residue yield, respectively 8.9 and 8.6 t ha‐1. The spatial analysis revealed that these three crops, which, according to our results, are feedstocks highly suitable a priori for second generation biofuels in the EU and are unevenly distributed across Europe. Weather fluctuation was identified as the major driver in residue production from cereals, while, in the case of starch crops and oilseeds – which are predominant in northern Europe – corresponded to the marked production trend likely influenced by the agricultural policies and agro‐management over the review period. Our results, among others, could help to understand and quantify the ecological boundaries of the bioeconomy from agriculture.     

Precise Gene Editing Preserves Hematopoietic Stem Cell Function following Transient p53-Mediated DNA Damage Response

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