CD8 + T Cells Exhibit an Exhausted Phenotype in Hemophagocytic Lymphohistiocytosis.

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome mainly caused by uncontrolled activation of antigen presenting cells and CD8 T cells. CD8 T cell exhaustion is a known phenomenon in chronic viral infections and cancer. However, the role of T cell exhaustion is not yet identified in HLH in the background of persistent inflammation. So, currently, we have characterized the CD8 T cells using flow cytometry to understand the phenomenon of exhaustion in these cells in HLH. METHODS: We have comprehensively evaluated lymphocyte subsets and characterized CD8 T cells using immunophenotypic markers like PD1, TIM3, LAG3, Ki67, Granzyme B, etc. in a cohort of 21 HLH patients. Effector cytokine secretion and degranulation by CD8 T cells are also studied. RESULTS: Our findings indicate skewed lymphocyte subsets and aberrantly activated CD8 T cells in HLH. CD8 T cells exhibit significantly increased expression of PD1, TIM3, and LAG3 prominently in primary HLH as compared to controls. PD1 + CD8 T cells express elevated levels of Granzyme B and Ki67. Moreover, CD8 T cells are hypofunctional as evidenced by significantly reduced cytokine secretion and compromised CD107a degranulation. CONCLUSION: The study has revealed that CD8 + cytotoxic T lymphocytes from HLH patients exhibited high expression of exhaustion markers with overall impaired function. To the best of our understanding, this is the first report suggesting functional exhaustion of CD8 T cells in both primary and secondary HLH. Future studies to understand the association of exhaustion with disease outcome are needed for its probable therapeutic implementation.

Reduction of radiation exposure to operating physician and assistant using a real-time auditory feedback dosimeter during femoral artery puncturing: a study on swine model.

BACKGROUND: Real-time dosimeters may create a relatively safer environment not only for the patient but also for the physician and the assistant as well. We propose the use of a real-time radiation measurement dosimeter having auditory feedback to reduce radiation exposure. METHODS: Radiation dose rates were measured for 30 fluoroscopy-guided puncturing procedures of femoral arteries in swine. Fifteen puncturing procedures were performed with real-time radiation measurement dosimeter having auditory feedback and other 15 were performed without auditory feedback dosimeter by an interventional cardiologist with 10 years of experience. RESULTS: The left body side of the operating physician (38%, p < 0.001) and assistant (25%, p < 0.001) was more exposed as compared to the right body side. Radiation dose rate to the left hand, left arm and left leg were reduced from 0.96 ± 0.10 to 0.79 ± 0.12 mSv/h (17% reduction, p < 0.001), from 0.11 ± 0.02 to 0.07 ± 0.01 mSv/h (36% reduction, p < 0.001) and from 0.22 ± 0.06 to 0.15 ± 0.02 mSv/h (31% reduction, p < 0.001) with the use of auditory feedback dosimeter, respectively. The mean fluoroscopic time was reduced from 4.8 ± 0.43 min to 4.2 ± 0.53 min (p < 0.001). The success rate of performing arterial puncturing was 100%. CONCLUSIONS: The use of auditory feedback dosimeter resulted in reduction in effective dose. The sound beep alerted the physician from the danger of exposure, and this approach induced awareness and protective mindset to the operating physician and assistant.

Reduction of operator radiation exposure using a passive robotic device during fluoroscopy-guided arterial puncture: an experimental study in a swine model.

BACKGROUND: Vascular interventions imply radiation exposure to the operating physician (OP). To reduce radiation exposure, we propose a novel passive robotic device for fluoroscopy-guided arterial puncturing. METHODS: X-ray dose rates were measured for a total of 30 fluoroscopy-guided puncture femoral arteries in 15 pigs. Fifteen punctures were performed with the device while the other 15 were performed without the device by an interventional cardiologist with 10 years of experience. Parametric t test was used. RESULTS: The success rate with the device was 100%. Overall, the OP received more radiation (0.41 mSv/h) as compared to the assistant (0.06 mSv/h) (p <  0.001) and, amongst OP's body parts, hands received more radiation than other body parts (p <  0.001). The radiation dose rate to the OP's hands during arterial puncturing performed manually without the device was 0.95 ± 0.25 mSv/h whereas it was 0.14 ± 0.006 mSv/h using the device, resulting in an 85% reduction (p <  0.001). For the head, the dose was reduced from 0.16 mSv/h to 0.08 mSv/h (50% reduction, p <  0.001), and for the dominant arm, from 0.12 mSv/h to 0.07 mSv/h (42% reduction, p <  0.001). The fluoroscopy time was reduced from 4.5 ± 0.15 min to 4.3 ± 0.11 min device (p = 0.002). CONCLUSIONS: In a swine model, fluoroscopy time and radiation exposure for the OP puncturing femoral artery were significantly reduced by using the passive robotic device.

Evolution of Single Chain Conformation for Model Comb-Like Chains with Grafting Density Ranging from 0 to ∼100% in Dilute Solution.

This work aims to experimentally clarify how the single chain conformation evolves as a function of grafting density for model comb-like chains in dilute solution in the whole density regime. Via a combination of rational design, precise synthesis and accurate characterization, we obtained four sets of PPANb-g-PS30-σ comb-like samples with well-defined architectures and accurately extracted their molecular parameters by triple detection size exclusion chromatography (TD-SEC). With these samples in hand, we quantified how the excluded volume interaction and chain conformation evolve with the grafting density (σ) in the whole density regime. Three main findings are reported: (i) the graft-graft excluded volume interaction is not ignorable even in the low σ-regime; (ii) contrary to theoretical predictions, both the excluded volume interaction and the chain conformation are found to be Nb-dependent; (iii) both Rg ∼ σ1/3 and [η] ∼ σ0 are experimentally confirmed for comb-like chains from different σ and Nb, signifying a unique 3D mass-size growth pattern and a quasi-3D fractal feature. The obtained results help clarify some long-existed controversial issues in the field.

Component Alignment in Simultaneous Bilateral versus Unilateral Total Knee Arthroplasty

PURPOSE: The purpose of this study was to investigate differences in component alignment between first and second knees in simultaneous bilateral total knee arthroplasty (SBTKA) and unilateral TKA (UTKA). MATERIALS AND METHODS: 274 SBTKAs and 198 UTKAs were included in study. Patients were divided into three groups as SBTKA on the right knee (group A), SBTKA on the left knee (group B) and UTKA (group C). Femoral and tibial component alignment was checked in both coronal plane (alpha [α] and beta [β] angles) and sagittal plane (gamma [γ] and delta [δ] angles) radiographs. RESULTS: There were no statistically significant differences among groups in the preoperative anatomical varus angle and Kellgren–Lawrence gonarthrosis classification grade (p=0.139 and p=0.329, respectively). In the coronal plane, the alignment of femoral component (α angle) and tibial component (β angle) was similar in all three groups (α angle, 95.01 vs. 95.14 vs. 94.9, p=0.945; β angle, 90.03 vs. 89.67 vs. 89.98, p=0.483). The sagittal plane alignment of femoral component (γ angle) and tibial component (δ angle) did not show significant differences (γ angle, 7.04 vs. 6.98 vs. 7.00, p=0.132; δ angle, 86.56 vs. 87.41 vs. 86.73, p=0.610). CONCLUSIONS: The angular alignment of components was similar between SBTKA and UTKA.

P4VP-RuII(bda) polyelectrolyte-metal complex as water oxidation catalyst: on the unique slow-diffusion and multi-charge effects of the polyelectrolyte ligand.

In this work, we analyze the catalytic mechanism of P4VP-RuII(bda) polyelectrolyte-metal complex (PMC) as a water oxidation catalyst and elucidate how the unique slow diffusion and multi-charge properties of the polyelectrolyte ligand dominate the catalytic process. Four poly(4-vinyl pyridine)-Ru(bda) (P4VP-Ru) PMCs with different chain lengths and controlled Ru loading amounts were prepared and used as catalysts for catalytic water oxidation. These catalysts present excellent catalytic performance with turnover numbers (TON) from ∼1200 to ∼1700 because of the good hydration properties. Surprisingly, the combined catalysis kinetics and kinetic isotope effect (KIE) studies for P4VP-Ru PMCs confirm the single-site water nucleophilic attack (WNA) mechanism in catalysis, rather than the interaction between two metal oxide units (I2M). A combination of dynamic light scattering characterization, zeta-potential measurement and molecular dynamics simulation reveals that the slow diffusion and multi-charge properties of the polyelectrolyte ligand are responsible for the observed mechanism difference between the P4VP-Ru PMC system and small-molecule multi-nuclear system, though the two systems actually own a similar structural feature (flexible linkages between Ru centers). Our experimental and simulation results highlight the fact that though the existence of flexible linkages between Ru centers could provide large conformation entropy for the occurrence of Ru-dimerization in small-molecule and neutral polymer systems, the entropy elasticity could not overcome the electrostatic interaction energy in the PMC system. Clearly, this work unambiguously clarified why both intra-chain and inter-chain Ru-dimerization (I2M) are prohibited for the PMC system from a perspective of macromolecular chemistry and physics.

Linear EBUS-guided fiducial marker placement to guide radiotherapy for endobronchial, radiographically occult synchronous primary squamous cell carcinoma of the lung.

Radiation therapy has emerged as a useful alternative therapy for patients with early-stage, non-resectable lung cancer. In patients whose malignancies are difficult to localize on computed tomography imaging, such therapy becomes difficult. Fiducial markers are frequently placed in peripheral pulmonary lesions to assist radiation therapy. Although placement of markers under linear endobronchial ultrasonography within mediastinal and hilar lymph nodes has been reported, no strategy has been described to assist radiotherapy of purely endobronchial tumors. We present a case of bilateral, unresectable, radiographically occult endobronchial squamous cell carcinoma treated with radiotherapy guided by fiducial markers placed under linear endobronchial ultrasonographic guidance. The patient subsequently underwent intensity-modified radiation therapy to both lesions with pathologic complete response. Linear endobronchial ultrasound is a promising tool for placement of markers to guide radiation therapy of these difficult-to-treat lesions.

Molecular memory with atomically smooth graphene contacts.

We report the use of bilayer graphene as an atomically smooth contact for nanoscale devices. A two-terminal bucky-ball (C60) based molecular memory is fabricated with bilayer graphene as a contact on the polycrystalline nickel electrode. Graphene provides an atomically smooth covering over an otherwise rough metal surface. The use of graphene additionally prohibits the electromigration of nickel into the C60 layer. The devices exhibit a low-resistance state in the first sweep cycle and irreversibly switch to a high-resistance state at 0.8 to 1.2 V bias. In the subsequent cycles, the devices retain the high-resistance state, thus making it write-once read-many memory.

Controlled synthesis of bilayer graphene on nickel.

We report a uniform and low-defect synthesis of bilayer graphene on evaporated polycrystalline nickel films. We used atmospheric pressure chemical vapor deposition with ultra-fast substrate cooling after exposure to methane at 1,000°C. The optimized process parameters, i.e., growth time, annealing profile and flow rates of various gases, are reported. By using Raman spectroscopy mapping, the ratio of 2D to G peak intensities (I2D/IG) is in the range of 0.9 to 1.6 over 96% of the 200 µm × 200 µm area. Moreover, the average ratio of D to G peak intensities (ID/IG) is about 0.1.