Natural killer cell–derived extracellular vesicles in cancer therapy

Cancer is a major cause of death in the industrialized world. New therapies are constantly being developed in order to reduce morbidity and mortality. NK cell–based cellular therapies have shown effect against haematological malignancies, but it has been difficult to target solid tumours due to low NK cell infiltration of the tumour and efficient tumour evasion strategies. NK cells release extracellular vesicles that naturally contain cytolytic proteins and tumour-targeting molecules. These vesicles can directly interact with and kill malignant cells, and their small size could allow more efficient extravasation into the tumour tissue. Extracellular vesicles are also less sensitive to the hostile tumour microenvironment compared to cells. Based on their features, NK cell–derived extracellular vesicles represent promising novel tools in oncology. In this review, we summarize the current available literature on NK cell–derived extracellular vesicles and discuss how they may be utilized in therapy for solid tumours.     

Calcium,Magnesium, and Zinc Supplementation during Pregnancy: The Additive Value of Micronutrients on Maternal Immune Response after SARS-CoV-2 Infection

Magnesium may contribute to the immune response during and after SARS-CoV-2 infection by acting as a cofactor for immunoglobulin production and other processes required for T and B cell activity. Considering magnesium as a recommended dietary supplement during pregnancy and the possible role of magnesium deficiency in COVID-19 and its complications, the current study sought to determine the effect of magnesium and magnesium-containing nutritional supplements on the immune response following SARS-CoV-2 infection in pregnant women, as well as to observe differences in pregnancy outcomes based on the supplements taken during pregnancy. The study followed a cross-sectional design, where patients with a history of SARS-CoV-2 infection during their pregnancy were surveyed for their preferences in nutritional supplementation and their profile compared with existing records from the institutional database. A cohort of 448 pregnant women with COVID-19 during 22 months of the pandemic was assembled, out of which 13.6% took a magnesium-only supplement, and 16.5% supplemented their diet with a combination of calcium, magnesium, and zinc. Around 60% of patients in the no-supplementation group had the SARS-CoV-2 anti-RBD lower than 500 U/mL, compared with 50% in those who took magnesium-based supplements. A quantity of magnesium >450 mg in the taken supplements determined higher levels of antibody titers after COVID-19. Low magnesium dosage (<450 mg) was an independent risk factor for a weak immune response (OR-1.25, p-value = 0.003). The observed findings suggest supplementing the nutritional intake of pregnant women with magnesium-based supplements to determine higher levels of SARS-CoV-2 anti-RBD antibodies, although causality remains unclear.     

Measuring the double-drift illusion and its resets with hand trajectories

If a Gabor pattern drifts in one direction while its internal texture drifts in the orthogonal direction, its perceived position deviates further and further away from its true path. We first evaluated the illusion using manual tracking. Participants followed the Gabor with a stylus on a drawing tablet that coincided optically with the horizontal monitor surface. Their hand and the stylus were not visible during the tracking. The magnitude of the tracking illusion corresponded closely to previous perceptual and pointing measures indicating that manual tracking is a valid measure for the illusion. This allowed us to use it in a second experiment to capture the behavior of the illusion as it eventually degrades and breaks down in single trials. Specifically, the deviation of the Gabor stops accumulating at some point and either stays at a fixed offset or resets toward the veridical position. To report the perceived trajectory of the Gabor, participants drew it after the Gabor was removed from the monitor. Resets were detected and analyzed and their distribution matches neither a temporal nor a spatial limit, but rather a broad gamma distribution over time. This suggests that resets are triggered randomly, about once per 1.3 seconds, possible by extraneous distractions or eye movements.     

The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting

The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low‐dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti‐inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non‐fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at‐risk groups include an HIV test, a QuantiFERON‐TB Gold test and a chest X‐ray. In patients without complications, repeat the FBC at 2–4 weeks, then every 3–6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low‐dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment‐emergent liver toxicity is related to underlying metabolic syndrome and non‐alcoholic fatty liver disease or non‐alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: ‘20 mg/day’ has been corrected to ‘20 gm/day’.] Although MTX is a potential teratogen post‐conception, there is little evidence for this pre‐conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri‐surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti‐tumour necrosis factor biologics.     

Use of the Falciform Ligament Flap for Closure of the Esophageal Hiatus in Giant Paraesophageal Hernia

OBJECTIVES: Laparoscopic repair of a giant paraesophageal hiatal hernia remains a challenging procedure. Several techniques have been developed in efforts to achieve tension-free reconstruction of the esophageal hiatus. In this report, we describe a technique whereby the falciform ligament is used as an autologous onlay flap to achieve tension-free closure of the crural defect of a giant paraesophageal hernia (GPEH). DISCUSSION: Use of the falciform ligament as a vascularized autologous onlay flap is a safe and effective procedure to obtain closure of the crural defect of a GPEH. The falciform ligament should be adequately mobilized from the anterior abdominal wall to prevent lateral tension on the flap, but care must be taken to avoid devascularization. Interrupted vertical mattress sutures are used to fix the falciform ligament to the left and right hiatal crurae.     

Computation of the Electrical Resistance of a Low Current Multi-Spot Contact

In high complexity electrical systems such as those used in the automotive industries, electric connectors play an important role. The automotive industry is gradually shifting its attention to electric cars, which means more electrical connectors for sensors and data collection. A fault in connectors for sensors used in a vehicle can cause drastic damage to capital equipment and, in the worst case, the loss of life. The studies of faults or degradation of electrical contacts are essential for safety in vehicles and various industries. Although such faults can be due to numerous factors (such as dust, humidity, mechanical vibration, etc.) and some yet to be discovered, high contact resistance is the main factor causing erratic behavior of electrical contacts. This paper presents a study on the computation of electrical contact resistance of two metal conductors (in the form of a disk) with analytical relations and a numerical computation model based on the finite element method (FEM) in COMSOL Multiphysics. The contact spots were considered to have a higher electrical resistivity value (ρ_cs) than those of the two metal conductors (ρ_Cu). Studies such as the one in view that is carried out on a microscopic level are often difficult to investigate experimentally. Therefore, with the help of a simplified numerical model, the consequences of the degradation of electrical contacts are investigated. To validate the FEM model, the numerical results were compared to those obtained from analytical models.     

Degradation of a chromogenic substrate by α2-macroglobulin from plasma of patients with rheumatoid arthritis

We have shown previously that serum from patients with rheumatoid arthritis (RA) contains a polyclonal B cell activator that is associated with α₂-macroglobulin (α₂M). Some biologic effects of this activator appear to be due to a trypsin-like protease attached to α₂M. Therefore, in the present study, we used an anti-α₂M antibody solid-phase assay, with Chromozym-Try as a substrate, to determine the level of α₂M-protease complexes in plasma α₂M. We found higher levels of these complexes in RA patients than in 2 control groups. Since α₂M-protease complexes have been shown to induce RA-like inflammation in experimental animals and to be produced by lymphoid cells, we speculate that they may be involved in the pathogenesis of RA. However, the role of the other cells or enzyme systems in the formation of these complexes has not yet been ruled out. Results of these investigations could lead to another link between activation of the immune system and joint inflammation.     

Twelve Weeks of Reversed Umbilical Flow in a Fetal Growth Restriction Case Associated with Severe Periconceptional Maternal Anemia

We present a case of a patient diagnosed with severe intrauterine growth restriction and periconceptional severe anemia, where the fetal well-being features, including reversal of umbilical artery end-diastolic flow and abnormal cerebroplacental ratio, remained stationary for 12 weeks. We are not aware of reports with similar findings, and the professionals should take into consideration the possibility of a “frozen” fetal well-being for a long time. Possibly, in our case, the evolution may be due to the prompt correction of the chronic severe maternal anemia. This approach may offer the opportunity to prolong the pregnancy, even in cases with apparently imminent delivery, as the association of reversal of umbilical artery end-diastolic flow.     

Full dynamics of a red blood cell in shear flow

At the cellular scale, blood fluidity and mass transport depend on the dynamics of red blood cells in blood flow, specifically on their deformation and orientation. These dynamics are governed by cellular rheological properties, such as internal viscosity and cytoskeleton elasticity. In diseases in which cell rheology is altered genetically or by parasitic invasion or by changes in the microenvironment, blood flow may be severely impaired. The nonlinear interplay between cell rheology and flow may generate complex dynamics, which remain largely unexplored experimentally. Under simple shear flow, only two motions, “tumbling” and “tank-treading,” have been described experimentally and relate to cell mechanics. Here, we elucidate the full dynamics of red blood cells in shear flow by coupling two videomicroscopy approaches providing multidirectional pictures of cells, and we analyze the mechanical origin of the observed dynamics. We show that contrary to common belief, when red blood cells flip into the flow, their orientation is determined by the shear rate. We discuss the “rolling” motion, similar to a rolling wheel. This motion, which permits the cells to avoid energetically costly deformations, is a true signature of the cytoskeleton elasticity. We highlight a hysteresis cycle and two transient dynamics driven by the shear rate: an intermittent regime during the “tank-treading-to-flipping” transition and a Frisbee-like “spinning” regime during the “rolling-to-tank-treading” transition. Finally, we reveal that the biconcave red cell shape is highly stable under moderate shear stresses, and we interpret this result in terms of stress-free shape and elastic buckling.