Three-dimensional two-layer collagen matrix gel culture model for evaluating complex biological functions of monocyte-derived dendritic cells

Dendritic cell-like cells (Mo-DCs) generated from peripheral blood monocytes with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used as tools to treat cancer patients (DC-vaccines). Because Mo-DCs have multiple antigen presentation-related functions, including phagocytosis, migration, cytokine production, and T cell stimulation, establishment of a method for simultaneously evaluating the various functions of Mo-DCs is important. We developed a new in vitro three-dimensional two-layer collagen matrix culture model that consists of a collagen gel containing Mo-DCs as the lower layer and a collagen gel containing necrotic GCTM-1 tumor cells and/or T cells as the upper layer. We used this system to observe simultaneously multiple functions of Mo-DCs by phase-contrast or fluorescence microscopy and to assess IL-12 secretion during more than 2 weeks of culture. We also observed interactions between Mo-DCs and necrotic GCTM-1 or T cells on an individual cell basis by time-lapse videomicroscopy. In addition, we collected Mo-DCs from the collagen gels by collagenase treatment and analyzed the expression of antigen presentation-related molecules such as HLA-DR, CD80, CD83, and CD86 on Mo-DCs. This model may be a useful tool for evaluation of the various functions of Mo-DCs used as DC vaccines and for studies of the complex behaviors of Mo-DCs in vivo.     

Magnetically suspended rotary blood pump with radial type combined motor-bearing

A magnetically suspended centrifugal blood pump is being developed with a combined motor-bearing for long-term ventricular assist systems. The combined motor-bearing actively suspends a rotor in a radial direction to deal with radial force unbalance in the pump and rotates the rotor by using the electric magnetic field. Therefore, the pump has no mechanical parts such as bearings of the motor and has a long lifetime. The developed pump consists of a thin rotor with a semi open-type 6 vane impeller and a stator to suspend and rotate the rotor. The rotor has 4-pole permanent magnets on the circumferential surface. The outer diameter and the thickness of the rotor are 60 mm and 8 mm, respectively. Axial movement and tilt of the rotor are restricted by passive stability based on the thin rotor structure. Radial movements of the rotor, such as levitation in radial direction and rotation, are controlled actively by using electric magnets of the stator. The electric magnet coils to produce levitation and rotation forces are constructed on the periphery stator. The p +/- 2-pole algorithm and the synchronous motor mechanism are adopted to levitate and rotate the rotor. The radial gap between the rotor and the stator is 1 mm. A closed-loop circuit filled with water was connected to the developed pump to examine the basic performance of the pump and the magnetic suspension system. Maximum rotational speed, flow rate, and head were 2,800 rpm, 11 L/min, and 270 mm Hg, respectively. The rotor with the impeller could be suspended completely during the entire pumping process. We conclude the pump with the combined motor-bearing has sufficient performance for the blood pump.     

Saccular cerebral aneurysms in young adults

BACKGROUND: The formation and rupture of cerebral aneurysms has been controversial. In order to clarify their nature, this study investigates the size and location of ruptured and unruptured aneurysms in young adults and the results of surgery. METHODS: The subjects of this study are 35 patients with ruptured and two with unruptured aneurysms. They range in age from 20 to 39 years. The size and location of their aneurysms were determined by angiographic measure of their maximal inner diameters. Direct surgery was performed on 34 patients with ruptured aneurysms and on one with an unruptured aneurysm. RESULTS: Ruptured aneurysms in young adults increase in number and size as they grow older. In young adults showing no atherosclerosis or hypertension, ruptured aneurysms occurred in locations and with a frequency found in patients with hypertension. In young adults, aneurysms in the internal carotid artery larger than 3.5 mm (Fisher's exact test; p < 0.05) and the anterior communicating artery showed a tendency to rupture. The surgery produced excellent results in young adults with grade I to III by Hunt and Kosnik classification, but extremely poor results for those with grade IV resulting from vasospasm (Fisher's exact test; p < 0.05). CONCLUSION: It is possible that aneurysms found in young adults might in fact have been present from childhood and adolescence, increasing sufficiently in size to rupture in the forties and fifties. Accordingly, while aneurysm formation may be related to fragile arterial walls, aneurysm rupture may be the result of aging factors such as hypertension and atherosclerosis. Even in young adults, vasospasm had an impact on the outcome of surgery.     

Significant accumulation of KRAS mutations in bronchiolar metaplasia-associated honeycomb lesions of interstitial pneumonia

Interstitial pneumonia (IP) is a major risk factor for lung adenocarcinoma (LADC). IP-related LADC predominantly develops in the bronchiolar metaplasia lining in honeycomb lesions. Kirsten rat sarcoma virus (KRAS) is the most common oncogene mutated in IP-related LADC. The present study examined the metaplastic epithelia in honeycomb lesions for KRAS mutations using digital droplet polymerase chain reaction (ddPCR), a sensitive method used to detect infrequent mutations. Significantly higher KRAS mutation variant allele frequencies (VAFs) were detected in the metaplastic lung epithelia from 13 patients with IP compared with those in 46 non-lesioned lung samples from patients without IP (G12V, P=0.0004, G12C, P=0.0181, and G12A, P=0.0234; Mann Whitney U test). Multivariate analyses revealed that higher KRAS G12V (logistic regression model; P=0.0133, odds ratio=7.11) and G12C (P=0.0191, odds ratio=5.81) VAFs in patients with IP were independent of confounding variables, such as smoking and age. In patients with IP, metaplastic epithelia exhibited significantly higher KRAS G12V and G12C VAFs compared with the non-lesioned counterparts (paired t-test; G12V, P=0.0158, G12C, P=0.0465). These results suggested that IP could increase KRAS mutations and supported the hypothesis that bronchiolar metaplasia could be a precursor for IP-related LADC.     

Antimicrobial second skin using copper nanomesh

The functional support and advancement of our body while preserving inherent naturalness is one of the ultimate goals of bioengineering. Skin protection against infectious pathogens is an application that requires common and long-term wear without discomfort or distortion of the skin functions. However, no antimicrobial method has been introduced to prevent cross-infection while preserving intrinsic skin conditions. Here, we propose an antimicrobial skin protection platform copper nanomesh, which prevents cross-infectionmorphology, temperature change rate, and skin humidity. Copper nanomesh exhibited an inactivation rate of 99.99% for Escherichia coli bacteria and influenza virus A within 1 and 10 min, respectively. The thin and porous nanomesh allows for conformal coating on the fingertips, without significant interference with the rate of skin temperature change and humidity. Efficient cross-infection prevention and thermal transfer of copper nanomesh were demonstrated using direct on-hand experiments.

The functional support and advancement of our body while preserving the inherent naturalness is one of the ultimate goals of bioengineering (1–4). A functional layer is placed on the skin to complement the intrinsic biological and interactive functions (5, 6) and to add functions that do not yet exist (7–9). During use, the second skin layer should completely exploit its function and underlay skin functions without deforming the skin or interfering with the skin’s external interaction. Materials and structures need to be conformal and mechanically similar to the skin to minimize the distortion of natural sensations and movements. In addition, the air and heat transfer on the skin must be unimpeded to obtain a natural and comfortable wear fit (10).Body protection that requires common and long-term wear is an application in which both functionality and naturalness are important. As the outermost layer connecting our body to the environment, the skin is exposed to physical damage, hazardous chemicals, and infectious pathogens (11, 12). Therefore, we add a protective layer on the skin that blocks or filters out external contaminants. This entails the isolation and accumulation of biochemical compounds, which can lead to self-contamination and the subsequent cross-contamination/infection by interacting with other objects. In contrast to chemical contamination, which is not self-reproductive, the biological contamination of infectious microbes, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a considerable issue to be addressed.By containing an antimicrobial material on the surface of the skin protective layer, cross-infection can be prevented in the long term. Unlike temporary rinsing or disinfection, the use of antibacterial or antiviral substances such as chemical or natural disinfectants and metal nanomaterials inhibits the growth of microorganisms on the surface (13–17). These materials are embedded in a complete covering polymer layer, such as gloves (18, 19), to isolate and protect both the inner and outer surfaces from the infection. To add breathability to the textile especially for the mask (13, 20, 21), many antibacterial fibers have been developed based on these materials. Moreover, various skin-attachable platforms with antimicrobial properties have been developed for convenient usage in daily lives. Antimicrobial nanofibers with conformal attachment to the skin have been developed for drug delivery, wound healing (22, 23), and electrophysiology (24, 25). In addition, stretchable and antibacterial hydrogels have been developed to allow more natural skin movement in wound-healing applications (26–28).However, there has been no practical skin protective solution to prevent cross-infection while preserving intrinsic skin conditions such as surface morphology, thermal transfer, and skin humidity. The thickening of the additional skin layer frequently results in a significant modification of the surface morphology, heat transfer, and the corresponding sensation. Thin layers have limited performance in terms of antimicrobial duration and speed. The skin coverage of polymer or hydrogel film blocks the transfer of air, moisture, and heat. In addition, the antimicrobial performance is focused on the skin side rather than the external side that affects cross-infection. Voids owing to the stiffness of the film or fiber and morphological differences compared to the skin further limit conformality, heat transfer, and water/air permeability (29).Here, we propose an antimicrobial skin protection platform copper nanomesh, which prevents cross-infection while minimizing modification of intrinsic skin properties such as interfacial morphology, temperature change rate, and skin humidity. The thin thickness and porous structure of the nanomesh allow conformal attachment to the fingertips, regardless of the mechanical and structural variations of the fingerprints, nails, and interfaces. To impart antimicrobial properties, copper, one of the most well-known antimicrobial (nano)materials (30–33), was coated with maintaining the nanomesh structure (copper nanomesh, from here onward). The measured inactivation rates of copper nanomesh against Escherichia coli bacteria and influenza virus A (H1N1) were 99.99% within 1 min and 10 min, respectively. It was found that the nanomesh structure contributed to the acceleration of bacterial inactivation compared to the copper film. Furthermore, it exhibited high biocompatibility with the skin cells and stable antibacterial performance even after long-term use (more than 6 h), including water immersion (more than 1 h).In addition, we investigated the naturalness of the copper nanomesh compared to that of the copper film and conventional gloves. As confirmed using the artificial skin and fingerprint recognition, the proposed copper nanomesh exhibited a higher conformability compared to that of the copper film. The copper nanomesh showed a high hydrophobicity to block external contaminants in solution while having high gas permeability and maintaining the skin humidity in a safe range. Additionally, the insertion of copper nanomesh did not affect the temperature change rate, which is important to maintain the sensation and comfort fit of the skin. Finally, the copper nanomesh was compared to the glove by wearing on our hands and interacting with various real-life objects. Using the proposed copper nanomesh, we successfully achieved an effective prevention of cross-infection and less-hindered thermal recognition of objects.     

Risk Factors for Complications Associated with Peripherally Inserted Central Catheters During Induction Chemotherapy for Acute Myeloid Leukemia

Objective Peripherally inserted central catheters (PICCs) are widely used in patients with hematologic malignancies. However, the risks of PICC-related complications during chemotherapy for acute myeloid leukemia (AML) are not fully understood. Methods We conducted a retrospective review of 128 adult patients with AML who received induction therapy by way of PICC insertion between 2012 and 2019. Results The median duration of PICC insertion was 30 days. The incidence rate of catheter-related bloodstream infection (CRBSI) was 2.4% at 30 days, and women were more likely to suffer from CRBSI than men. Local reactions at the insertion site were observed in 56 patients; however, these events did not predict CRBSI. The incidence rates of catheter-related thrombosis (CRT) were 1.6% at 30 days. Obesity put patients at an increased risk for CRT. Unexpected PICC removal occurred in 59 patients, and women were at a higher risk of catheter removal than men. Conclusion Low PICC-related complication rates, possibly associated with high rates of catheter removal, were observed during intensive chemotherapy for AML. Women and obese patients require careful monitoring of their PICC. Procedures to achieve appropriate PICC removal without increasing the complication rate need to be considered.     

The effect of landiolol on cerebral blood flow in patients undergoing off-pump coronary artery bypass surgery

Purpose  

To examine the effect of landiolol on cerebral blood flow in patients with normal or deteriorated cardiac function.     

Cardiac anesthesia induction by low target plasma concentration setting of propofol using target-controlled infusion

BACKGROUND: Propofol-anesthesia administerd using target-controlled infusion (TCI) has been proposed for cardiac surgery. But, moderate target concentration of propofol during induction using TCI has not been studied in detail. METHODS: Thirty patients scheduled for cardiac surgery under cardiopulmonary bypass (CPB) and TCI propofol anesthesia were randomly divided into two groups to receive a computer-controlled infusion of propofol with target concentrations of 1.5 or 2.0 micro/g x ml(-1) [1.5 microg x ml(-1) group (n=15) and 2.0 microg x ml(-1) group (n=15)]. Mean arterial pressure (MAP), heart rate (HR) and bispectral index scale (BIS) values were recorded at 5 time points during induction of anesthesia. RESULTS: MAP was significantly lower in 2.0 microg x ml(-1) group compared with 1.5 microg x ml(-1) group. In both groups, a rise of BIS value did not occur during tracheal intubation. CONCLUSIONS: We have demonstrated that propofol TCI at a target concentration of 1.5 microg x ml(-1) is effective for hemodynamic stability during induction of anesthesia in patients for cardiac surgery under CPB.     

Recurrence of convexity meningiomas: tumor cells in the arachnoid membrane.

BACKGROUND: It remains open to debate why totally removed benign meningiomas recur. Two recurrent cases forced us to reconsider something corresponding to their recurrence that we had overlooked during Simpson grade I surgery. METHODS: This study is based on 24 recent and 9 earlier cases in which benign convexity meningiomas were totally removed by Simpson's grade I surgery. Tough or thick arachnoid membranes continuing to normal arachnoid membranes and contiguous to meningiomas but different from dura mater were encountered in 11 recent and at least 2 earlier cases. Such thick arachnoid membranes were left in place or only partially resected in two earlier cases but extensively resected in all recent cases. RESULTS: Light microscopy showed clusters of meningioma cells not in the removed dura mater but in the thick arachnoid membranes of an earlier case and 10 out of the 11 recent cases. Six and twelve years after initial surgery, recurrence of the 2 earlier cases was confirmed at subsequent surgery or diagnosed by neuro-imaging. By contrast, neuro-imaging from 30 to 132 months after initial surgery showed no recurrence in the 10 recent cases. A follow-up study over 5 years showed a significant difference in recurrence between Simpson's grade I surgery with and without extensive removal of surrounding thick arachnoid membranes (Fisher's exact test: p < 0.05). CONCLUSION: This study emphasizes the possibility that thick arachnoid membranes contiguous to meningiomas and continuous to normal arachnoid membranes, involving clusters of tumor cells, may relate to meningioma recurrence.     

The effect of landiolol on hemodynamics and left ventricular function in patients with coronary artery disease

STUDY OBJECTIVE: To examine the effect of landiolol (normal dose) on hemodynamics and left ventricular (LV) function. DESIGN: Prospective, observational, repeated-measures study. SETTING: University hospital. PATIENTS: 56 adult patients who were diagnosed with angina pectoris and who underwent elective off-pump coronary artery bypass surgery. INTERVENTIONS: Patients were divided into two groups based on a preoperative LV ejection fraction (EF) 50% or higher (normal EF group, n = 28) and lower than 50% (low EF group, n = 28). Hemodynamics and LV function were recorded using a pulmonary artery catheter and transesophageal echocardiography at three time points (before administration of landiolol, immediately before completion of administration, and 15 minutes after completion of administration). MEASUREMENTS: Individual hemodynamic data were obtained using a pulmonary artery catheter, and individual parameters were determined from LV short-axis views in transesophageal echocardiography. MAIN RESULTS: Mean preoperative EFs were 57% +/- 5% and 47% +/- 3% in the normal and low EF groups, respectively. In both groups, landiolol produced a significant decrease in heart rate (HR), which then returned to baseline 15 minutes after completion of administration. A significant decrease in mean arterial pressure occurred in the low EF group, but the decrease was within 30% of baseline. In the normal EF group, there was no decrease in cardiac index, but a significant increase in stroke index, in addition to an increase in stroke volume. In the low EF group, cardiac index significantly decreased along with the decrease in HR, but there was no increase in end-diastolic volume or stroke volume. CONCLUSIONS: Administration of landiolol using the presently recommended dosage and administration route causes a decrease in HR without aggravation of hemodynamics in patients with normal cardiac function, but in patients with preoperative EF lower than 50%, it may lead to further deterioration of cardiac function due to a decrease in HR.