Point of care ultrasound (POCUS) telemedicine project in rural Nicaragua and its impact on patient management

Background

Point of care ultrasound (POCUS) is a useful diagnostic tool in medicine. POCUS provides an easy and reproducible method of diagnosis where conventional radiologic studies are unavailable. Telemedicine is also a great means of communication between educators and students throughout the world.

Hypothesis

Implementing POCUS with didactics and hands-on training, using portable ultrasound devices followed by telecommunication training, will impact the differential diagnosis and patient management in a rural community outside the United States.

Materials and methods

This is an observational prospective study implementing POCUS in Las Salinas, a small village in rural western Nicaragua. Ultrasound was used to confirm a diagnosis based on clinical exam, or uncover a new, previously unknown diagnosis. The primary endpoint was a change in patient management. International sonographic instructors conducted didactic and practical training of local practitioners in POCUS, subsequently followed by remote guidance and telecommunication for 3 months.

Results

A total of 132 patients underwent ultrasound examination. The most common presentation was for a prenatal exam (23.5 %), followed by abdominal pain (17 %). Of the 132 patients, 69 (52 %) were found to have a new diagnosis. Excluding pregnancy, 67 patients of 101 (66 %) were found to have a new diagnosis. A change in management occurred in a total of 64 (48 %) patients, and 62 (61 %) after excluding pregnancy.

Conclusion

Implementing POCUS in rural Nicaragua led to a change in management in about half of the patients examined. With the appropriate training of clinicians, POCUS combined with telemedicine can positively impact patient care.     

Embolic protection device use and its association with procedural safety and long‐term outcomes following saphenous vein graft intervention: An analysis from the British Columbia Cardiac registry

• Coronary stents are commonly deployed using high pressure. However, the duration time of balloon inflation during deployment is still to be determined.
• Vallurupalli and coworkers, in this issue of CCI, show that the stent system takes an average of 33 sec to “accommodate” its pressure during in vitro deployment. In patients, the mean stent inflation time to achieve pressure stability was 104 seconds, ranging from 30 to 380 sec.
• These results challenge a rapid inflation/deflation approach for stent deployment. It is suggested that the duration of the inflation might be individualized, in a case‐by‐case approach.
• However, the findings must be interpreted with caution, as they cannot be directly extrapolated to more diverse clinical, angiographic, and interventional scenarios.

     

Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation

Activation of CD4⁺ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4⁺ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4⁺ T cell populations in murine models and determined that inflammatory Teffs maintain high expression of glycolytic genes and rely on high glycolytic rates, while Tregs are oxidative and require mitochondrial electron transport to proliferate, differentiate, and survive. Metabolic profiling revealed that pyruvate dehydrogenase (PDH) is a key bifurcation point between T cell glycolytic and oxidative metabolism. PDH function is inhibited by PDH kinases (PDHKs). PDHK1 was expressed in Th17 cells, but not Th1 cells, and at low levels in Tregs, and inhibition or knockdown of PDHK1 selectively suppressed Th17 cells and increased Tregs. This alteration in the CD4⁺ T cell populations was mediated in part through ROS, as N-acetyl cysteine (NAC) treatment restored Th17 cell generation. Moreover, inhibition of PDHK1 modulated immunity and protected animals against experimental autoimmune encephalomyelitis, decreasing Th17 cells and increasing Tregs. Together, these data show that CD4⁺ subsets utilize and require distinct metabolic programs that can be targeted to control specific T cell populations in autoimmune and inflammatory diseases.     

Adipokines and proinflammatory cytokines,the key mediators in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.     

Thermotropic liquid crystals from biomacromolecules

Complexation of biomacromolecules (e.g., nucleic acids, proteins, or viruses) with surfactants containing flexible alkyl tails, followed by dehydration, is shown to be a simple generic method for the production of thermotropic liquid crystals. The anhydrous smectic phases that result exhibit biomacromolecular sublayers intercalated between aliphatic hydrocarbon sublayers at or near room temperature. Both this and low transition temperatures to other phases enable the study and application of thermotropic liquid crystal phase behavior without thermal degradation of the biomolecular components.Liquid crystals (LCs) play an important role in biology because their essential characteristic, the combination of order and mobility, is a basic requirement for self-organization and structure formation in living systems (1–3). Thus, it is not surprising that the study of LCs emerged as a scientific discipline in part from biology and from the study of myelin figures, lipids, and cell membranes (4). These and the LC phases formed from many other biomolecules, including nucleic acids (5, 6), proteins (7, 8), and viruses (9, 10), are classified as lyotropic, the general term applied to LC structures formed in water and stabilized by the distinctly biological theme of amphiphilic partitioning of hydrophilic and hydrophobic molecular components into separate domains. However, the principal thrust and achievement of the study of LCs has been in the science and application of thermotropic materials, structures, and phases in which molecules that are only weakly amphiphilic exhibit LC ordering by virtue of their steric molecular shape, flexibility, and/or weak intermolecular interactions [e.g., van der Waals and dipolar forces (11)]. These characteristics enable thermotropic LCs (TLCs) to adopt a wide variety of exotic phases and to exhibit dramatic and useful responses to external forces, including, for example, the electro-optic effects that have led to LC displays and the portable computing revolution. This general distinction between lyotropic LCs and TLCs suggests there may be interesting possibilities in the development of biomolecular or bioinspired LC systems in which the importance of amphiphilicity is reduced and the LC phases obtained are more thermotropic in nature. Such biological TLC materials are very appealing for several reasons. Most biomacromolecules were extensively characterized in aqueous environments, but in TLC phases, their solvent-free properties and functions could be investigated in a state in which no or only traces of water are present. Water exhibits a high dielectric constant and has the ability to form hydrogen bonds, greatly influencing the structure and functions of biomacromolecules or compromising electronic properties such as charge transport (12–15). Indeed, anhydrous TLC systems containing glycolipids (16–19), ferritin (20), and polylysine have been reported (21–23). However, a general approach to fabricating TLCs based on nucleic acids, polypeptides, proteins, and protein assemblies of large molecular weights such as virus particles remains elusive.Here we propose that the combination of biomaterials with suitably chosen surfactants, followed by dehydration, can be effectively applied as a simple generic scheme for producing biomacromolecular-based TLCs. We demonstrate that biological TLCs can be made from a remarkable range of biomolecules and bio-inspired molecules, including nucleic acids, polypeptides, fusion proteins, and viruses. TLC materials typically combine rigid or semirigid anisometric units, which introduce orientational anisotropy, with flexible alkyl chains, which suppress crystallization (24). In the present experiments, negatively charged biomolecules and bio-inspired molecules act as rigid parts, and cationic surfactants make up the flexible units to produce TLC phases with remarkably low LC-isotropic clearing temperatures, which is another TLC signature. Electrostatic interactions couple these rigid and flexible components into hybrid assemblies, which then order into lamellar phases of alternating rigid and flexible layers (Fig. 1) stabilized by the tendency in TLCs for rigid and flexible to spatially segregate (25).Open in a separate windowFig. 1.Proposed structures of TLCs formed by the biological building blocks complexed with surfactants, showing sketches of various lamellar phases and the corresponding phase transition temperatures (°C). The lamellar bilayer structures are made of, alternately, a sublayer of the biomacromolecules and an interdigitated sublayer of the surfactants, where the negatively charged parts of the biomolecules (e.g., phosphate groups of ssDNA and ssRNA, glutamate residues of supercharged ELPs, and N-terminal glutamate and aspartate residues of pVIII protein in phages) electrostatically interact with the cationic head groups of the surfactants. For the ssDNA–DOAB and ssRNA–DOAB smectic TLCs, the oligonucleotides are randomly orientated in the DNA (RNA) sublayers. For the ELP–DDAB complexes, in addition to the bilayer smectic phase, a modulated smectic (Sm_mod) phase is observed at lower temperature. For the phage–DOAB–DDAB lamellar structures, rodlike virus particles are embedded in a sublayer between interdigitated surfactants with additional in-plane orientational order.