Carpal tunnel syndrome secondary to tumoral calcinosis: a case report and review of the literature.

BACKGROUND: Carpal Tunnel Syndrome (CTS) is the most prevalent peripheral nerve entrapment disease. Its pathophysiology is multifactorial and defined as idiopathic in most cases. We present a rare case of CTS secondary to tumoral calcinosis and then searched the English literature to present the details of all published cases with this entity. CASE PRESENTATION: A 52-year-old woman presented for a one-year history of numbness and paresthesia in her right hand. The patient's signs, symptoms, physical examination, and nerve electrodiagnostic testing suggested median nerve compression at the level of the carpal tunnel. However, a confirmatory magnetic resonance imaging of the wrist showed a localized calcareous lesion in the carpal tunnel. Subsequently, carpal tunnel release and mass excision were successfully performed with no recurrence at a 3-month interval. CONCLUSION: CTS secondary to tumoral calcinosis is a rare benign condition. Physicians should remain vigilant and include it in their differential diagnosis when facing a previously healthy patient presenting for chronic CTS symptoms.

A Fibrin-Thrombin Based In Vitro Perfusion System to Study Flow-Related Prosthetic Heart Valves Thrombosis.

Prosthetic heart valve (PHV) replacement has increased the survival rate and quality of life for heart valve-diseased patients. However, PHV thrombosis remains a critical problem associated with these procedures. To better understand the PHV flow-related thrombosis problem, appropriate experimental models need to be developed. In this study, we present an in vitro fibrin clot model that mimics clot accumulation in PHVs under relevant hydrodynamic conditions while allowing real-time imaging. We created 3D-printed mechanical aortic valve models that were inserted into a transparent glass aorta model and connected to a system that simulates human aortic flow pulse and pressures. Thrombin was gradually injected into a circulating fibrinogen solution to induce fibrin clot formation, and clot accumulation was quantified via image analysis. The results of valves positioned in a normal versus a tilted configuration showed that clot accumulation correlated with the local flow features and was mainly present in areas of low shear and high residence time, where recirculating flows are dominant, as supported by computational fluid dynamic simulations. Overall, our work suggests that the developed method may provide data on flow-related clot accumulation in PHVs and may contribute to exploring new approaches and valve designs to reduce valve thrombosis.

Whole-genome sequence analysis of carbapenem-resistant Enterobacteriaceae recovered from hospitalized patients.

OBJECTIVES: Carbapenems are among the few effective antibiotics against multidrug-resistant Enterobacteriaceae. This study aimed at characterizing the plasmid content and resistome of clinical carbapenem-resistant Enterobacteriaceae (CRE) recovered from 2016 to 2019 from hospitalized patients in Lebanon. METHODS: Plasmid typing and whole-genome sequencing were used to study the genomic characteristics of 65 clinical CREs including 27 Escherichia coli, 24 Klebsiella pneumoniae, one Klebsiella quasipneumoniae, three Morganella morganii, three Citrobacter freundii, five Enterobacter hormaechei, and two Serratia marcescens. RESULTS: blaOXA-48 (33.8%; n = 22) and blaOXA-48-like genes were among the detected resistance determinants, with two isolates co-harbouring blaNDM-5. Various blaNDM variants, blaNDM-1 (16.9%; n = 11), blaNDM-5 (9.2%; n = 6), blaNDM-7 (9.2%; n = 6), and blaNDM-19 (4.6%; n = 3), different ESBLs, and AmpC ß-lactamases were detected. Carbapenem resistance determinants were linked to a variety of incompatibility groups with IncFIB(K) (43.1%; n = 28) being the most prevalent, followed by IncFIA (40.0%), IncL (35.4%), IncX3 (32.3%), IncI1 (32.3%), and IncFIIK (29.2%). CONCLUSIONS: We analysed the clonality and resistance determinants of 65 multidrug-resistant (MDR) Enterobacteriaceae recovered in the period from 2016 to 2019 from a large tertiary hospital in Lebanon. NDM variants, OXA-48, and OXA-181 were the most prevalent detected carbapenemases and were mostly linked to the dissemination of IncL, IncX3, and IncF. This study reinforces the need to track the spread and dominance of clinically relevant carbapenemase-encoding plasmids in healthcare settings.

In Vitro 3D Cell-Cultured Arterial Models for Studying Vascular Drug Targeting Under Flow.

The use of three-dimensional (3D) models of human arteries, which are designed with the correct dimensions and anatomy, enables the proper modeling of various important processes in the cardiovascular system. Recently, although several biological studies have been performed using such 3D models of human arteries, they have not been applied to study vascular targeting. This paper presents a new method to fabricate real-sized, reconstructed human arterial models using a 3D printing technique, line them with human endothelial cells (ECs), and study particle targeting under physiological flow. These models have the advantage of replicating the physiological size and conditions of blood vessels in the human body using low-cost components. This technique may serve as a new platform for studying and understanding drug targeting in the cardiovascular system and may improve the design of new injectable nanomedicines. Moreover, the presented approach may provide significant tools for the study of targeted delivery of different agents for cardiovascular diseases under patient-specific flow and physiological conditions.

Synthetic neural-like computing in microbial consortia for pattern recognition.

Complex biological systems in nature comprise cells that act collectively to solve sophisticated tasks. Synthetic biological systems, in contrast, are designed for specific tasks, following computational principles including logic gates and analog design. Yet such approaches cannot be easily adapted for multiple tasks in biological contexts. Alternatively, artificial neural networks, comprised of flexible interactions for computation, support adaptive designs and are adopted for diverse applications. Here, motivated by the structural similarity between artificial neural networks and cellular networks, we implement neural-like computing in bacteria consortia for recognizing patterns. Specifically, receiver bacteria collectively interact with sender bacteria for decision-making through quorum sensing. Input patterns formed by chemical inducers activate senders to produce signaling molecules at varying levels. These levels, which act as weights, are programmed by tuning the sender promoter strength Furthermore, a gradient descent based algorithm that enables weights optimization was developed. Weights were experimentally examined for recognizing 3 × 3-bit pattern.

Advanced microfluidic droplet manipulation based on piezoelectric actuation.

As droplet-based microfluidic devices evolve, the demand for simple-to-fabricate droplet manipulation modules increases. Of these modules, droplet sorting has drawn much attention due to its ability not only to enrich, but also to selectively isolate droplet subpopulations of interest. In this paper, we present an innovative piezoelectric-driven droplet sorter that is simple to fabricate, reproducible and robust, which provides extensive control over spatio-temporal droplet pattern. This degree of control is demonstrated by sorting droplets of alternating volumes and by grouping defined number of droplets into traveling clusters. The ability to automatically sort droplets is demonstrated by computerized detection and sorting of droplets based on their color. The sorter performance was investigated and found to work on a wide range of sorting parameters. The sorter is created by a single step fabrication process and does not rely on complex electronics or optics. These advantages simplify the adoption of droplet-based microfluidic technology by the scientific community and provide an ideal platform for single cell assays.

A microfluidic traps system supporting prolonged culture of human embryonic stem cells aggregates.

The unlimited proliferative and differentiative capacities of embryonic stem cells (ESCs) are tightly regulated by their microenvironment. Local concentrations of soluble factors, cell-cell interactions and extracellular matrix signaling are just a few variables that influence ESC fate. A common method employed to induce ESC differentiation involves the formation of cell aggregates called embryoid bodies (EBs), which recapitulate early stages of embryonic development. EBs are normally formed in suspension cultures, producing heterogeneously shaped and sized aggregates. The present study demonstrates the usage of a microfluidic traps system which supports prolonged EB culturing. The traps are uniquely designed to facilitate cell capture and aggregation while offering efficient gas/nutrients exchange. A finite element simulation is presented with emphasis on several aspects critical to appropriate design of such bioreactors for ESC culture. Finally, human ESC, mouse Nestin-GFP ESC and OCT4-EGFP ESCs were cultured using this technique and demonstrated extended viability for more than 5 days. In addition, EBs developed and maintained a polarized differentiation pattern, possibly as a result of the nutrient gradients imposed by the traps bioreactor. The novel microbioreactor presented here can enhance future embryogenesis research by offering tight control of culturing conditions.

Mapping deposition of particles in reconstructed models of human arteries.

Targeted drug delivery to diseased vasculature, such as atherosclerotic lesions, is a multistep process, which is based on the transport of drug carriers to a selected region and their deposition at the desired destination. Current modeling approaches, including microfluidics and animal models, fail to accurately simulate this multi-scale process in human arteries, where blood flow is dominant. Here we study particle deposition in endothelialized 3D reconstructed models of the human carotid bifurcation under physiological hemodyamic conditions. Our results showed that particle localization is highly dependent on vessel geometry and local flow features. Additionally, while strongly adhesive particles tend to adhere more profoundly at high-shear regions, associated with athero-thrombosis, enhanced deposition at vascular flow regions, associated with inflammation and plaque accumulation, e.g., recirculation flows, can be achieved using weakly adhesive particles. Moreover, pulsatile flow as well as presence of blood cells significantly reduce particle adhesion and affect their deposition pattern. These findings highlight the key role of vessel geometry, hemodynamics and particle characteristics in the optimizing vascular targeting nano-carriers.

Targeting functionalized nanoparticles to activated endothelial cells under high wall shear stress.

Local inflammation of the endothelium is associated with a plethora of cardiovascular diseases. Vascular-targeted carriers (VTCs) have been advocated to provide focal effective therapeutics to these disease sites. Here, we examine the design of functionalized nanoparticles (NPs) as VTCs that can specifically localize at an inflamed vessel wall under pathological levels of high shear stress, associated for example with clinical (or in vivo) conditions of vascular narrowing and arteriogenesis. To test this, carboxylated fluorescent 200 nm polystyrene particles were functionalized with ligands to activated endothelium, that is, an E-selectin binding peptide (Esbp), an anti ICAM-1 antibody, or using a combination of both. The functionalized NPs were investigated in vitro using microfluidic models lined with inflamed (TNF-α stimulated) and control endothelial cells (EC). Specifically, their adhesion was monitored under different relevant wall shear stresses (i.e., 40-300 dyne/cm2) via real-time confocal microscopy. Experiments reveal a significantly higher specific adhesion of the examined functionalized NPs to activated EC for the window of examined wall shear stresses. Moreover, particle adhesion correlated with the surface coating density whereby under high surface coating (i.e., ~10,000 molecule/particle), shear-dependent particle adhesion increased significantly. Altogether, our results show that functionalized NPs can be designed to target inflamed endothelial cells under high shear stress. Such VTCs underscore the potential for attractive avenues in targeting drugs to vasoconstriction and arteriogenesis sites.

A microfluidic droplet generator based on a piezoelectric actuator.

Droplet based microfluidic systems have been shown to be most valuable in biology and chemistry research. However droplet modulation and manipulation requires still further improvement in order to make this technology feasible particularly for biological applications. On demand generation of droplets and droplet synchronization, which is crucial for coalescence, remain largely unanswered. The present study describes a simple and robust droplet generator based on a piezoelectric actuator which is integrated into a microfluidic device. The droplet generator is able to independently control the droplet size, rate of formation and distance between droplets. Moreover, the droplet uniformity is especially high, deviating from the mean value by less than 0.3%. The cross flow and T-junction configurations are tested and show no significant differences, yet the inlet to main channel ratio is found to be important. As this ratio increases, droplets tend to be generated in bursts instead of individually. The physical mechanisms involved are discussed, providing insight into optimized design of such systems.

Design of well and groove microchannel bioreactors for cell culture.

Microfluidic bioreactors have been shown valuable for various cellular applications. The use of micro-wells/grooves bioreactors, in which micro-topographical features are used to protect sensitive cells from the detrimental effects of fluidic shear stress, is a promising approach to culture sensitive cells in these perfusion microsystems. However, such devices exhibit substantially different fluid dynamics and mass transport characteristics compared to conventional planar microchannel reactors. In order to properly design and optimize these systems, fluid and mass transport issues playing a key role in microscale bioreactors should be adequately addressed. The present work is a parametric study of micro-groove/micro-well microchannel bioreactors. Operation conditions and design parameters were theoretically examined via a numerical model. The complex flow pattern obtained at grooves of various depths was studied and the shear protection factor compared to planar microchannels was evaluated. 3D flow simulations were preformed in order to examine the shear protection factor in micro-wells, which were found to have similar attributes as the grooves. The oxygen mass transport problem, which is coupled to the fluid mechanics problem, was solved for various groove geometries and for several cell types, assuming a defined shear stress limitation. It is shown that by optimizing the groove depth, the groove bioreactor may be used to effectively maximize the number of cells cultured within it or to minimize the oxygen gradient existing in such devices. Moreover, for sensitive cells having a high oxygen demand (e.g., hepatocytes) or low endurance to shear (e.g., human embryonic stem cells), results show that the use of grooves is an enabling technology, since under the same physical conditions the cells cannot be cultured for long periods of time in a planar microchannel. In addition to the theoretical model findings, the culture of human foreskin fibroblasts in groove (30 microm depth) and well bioreactors (35 microm depth) was experimentally examined at various flow rates of medium perfusion and compared to cell culture in regular flat microchannels. It was shown that the wells and the grooves enable a one order of magnitude increase in the maximum perfusion rate compared to planar microchannels. Altogether, the study demonstrates that the proper design and use of microgroove/well bioreactors may be highly beneficial for cell culture assays.