Microvascular oxygen consumption during sickle cell pain crisis.

Sickle cell disease is an inherited blood disorder characterized by chronic hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in the microvasculature, a process dependent on the concentration of hemoglobin S and the rate of deoxygenation, among other factors. We measured oxygen consumption in the thenar eminence during brachial artery occlusion in sickle cell patients and healthy individuals. Microvascular oxygen consumption was greater in sickle cell patients than in healthy individuals (median [interquartile range]; sickle cell: 0.91 [0.75-1.07] vs healthy: 0.75 [0.62-0.94] -ΔHbO2/min, P < .05) and was elevated further during acute pain crisis (crisis: 1.10 [0.78-1.30] vs recovered: 0.88 [0.76-1.03] -ΔHbO2/min, P < .05). Increased microvascular oxygen consumption during pain crisis could affect the local oxygen saturation of hemoglobin when oxygen delivery is limiting. Identifying the mechanisms of elevated oxygen consumption during pain crisis might lead to the development of new therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT01568710.

Solvation structure of the halides from x-ray absorption spectroscopy.

Three-dimensional models for the aqueous solvation structures of chloride, bromide, and iodide are reported. K-edge extended X-ray absorption fine structure (EXAFS) and Minuit X-ray absorption near edge (MXAN) analyses found well-defined single shell solvation spheres for bromide and iodide. However, dissolved chloride proved structurally distinct, with two solvation shells needed to explain its strikingly different X-ray absorption near edge structure (XANES) spectrum. Final solvation models were as follows: iodide, 8 water molecules at 3.60 ± 0.13 Å and bromide, 8 water molecules at 3.40 ± 0.14 Å, while chloride solvation included 7 water molecules at 3.15 ± 0.10 Å, and a second shell of 7 water molecules at 4.14 ± 0.30 Å. Each of the three derived solvation shells is approximately uniformly disposed about the halides, with no global asymmetry. Time-dependent density functional theory calculations simulating the chloride XANES spectra following from alternative solvation spheres revealed surprising sensitivity of the electronic state to 6-, 7-, or 8-coordination, implying a strongly bounded phase space for the correct structure during an MXAN fit. MXAN analysis further showed that the asymmetric solvation predicted from molecular dynamics simulations using halide polarization can play no significant part in bulk solvation. Classical molecular dynamics used to explore chloride solvation found a 7-water solvation shell at 3.12 (-0.04/+0.3) Å, supporting the experimental result. These experiments provide the first fully three-dimensional structures presenting to atomic resolution the aqueous solvation spheres of the larger halide ions.

Vasculopathy, inflammation, and blood flow in leg ulcers of patients with sickle cell anemia.

Chronic leg ulcers are frequent and debilitating complications of sickle cell anemia. Inadequate blood supply has been postulated to be an important factor in their occurrence and delayed healing. Little is known about their microcirculatory and histopathological changes. We evaluated the microcirculation of lower extremity ulcers with laser speckle contrast imaging and infrared thermography and obtained clinical and laboratory characteristics in 18 adults with sickle cell anemia and chronic leg ulcers. Skin biopsies were obtained in four subjects. Subjects had markers of severe disease, anemia, high degree of hemolysis, inflammation, and thrombophilia. The highest blood flow was present in the ulcer bed, progressively less in the immediate periwound area, and an unaffected control skin area in the same extremity. Microscopic examination showed evidence of venostasis, inflammation, and vasculopathy. Blood vessels were increased in number, had activated endothelium and evidence of thrombosis/recanalization. High blood flow may be due to chronic inflammation, cutaneous vasodilatation, venostasis, and in situ thrombosis. These changes in skin microcirculation are similar to chronic venous ulcers in the non-sickle cell disease (SCD) population, thus suggesting that leg ulcers may be another end-organ complication with endothelial dysfunction that appears in patients with SCD at a younger age and with higher frequency than in the general population.

Transformer based Generative Adversarial Network for Liver Segmentation.

Automated liver segmentation from radiology scans (CT, MRI) can improve surgery and therapy planning and follow-up assessment in addition to conventional use for diagnosis and prognosis. Although convolutional neural networks (CNNs) have became the standard image segmentation tasks, more recently this has started to change towards Transformers based architectures because Transformers are taking advantage of capturing long range dependence modeling capability in signals, so called attention mechanism. In this study, we propose a new segmentation approach using a hybrid approach combining the Transformer(s) with the Generative Adversarial Network (GAN) approach. The premise behind this choice is that the self-attention mechanism of the Transformers allows the network to aggregate the high dimensional feature and provide global information modeling. This mechanism provides better segmentation performance compared with traditional methods. Furthermore, we encode this generator into the GAN based architecture so that the discriminator network in the GAN can classify the credibility of the generated segmentation masks compared with the real masks coming from human (expert) annotations. This allows us to extract the high dimensional topology information in the mask for biomedical image segmentation and provide more reliable segmentation results. Our model achieved a high dice coefficient of 0.9433, recall of 0.9515, and precision of 0.9376 and outperformed other Transformer based approaches. The implementation details of the proposed architecture can be found at https://github.com/UgurDemir/tranformer_liver_segmentation.

Gallbladder: Role of Interventional Radiology.

Percutaneous cholecystostomy is an established procedure for the management of patients with acute cholecystitis and with significant medical comorbidities that would make laparoscopic cholecystectomy excessively risky. In this review, we will explore the role of percutaneous cholecystostomy in the management of acute cholecystitis as well as other applications in the management of biliary pathology. The indications, grading, technical considerations, and postprocedure management in the setting of acute cholecystitis are discussed. In addition, we will discuss the potential role of percutaneous cholecystostomy in the management of gallstones and biliary strictures, in establishing internal biliary drainage, and in a joint setting with other clinicians such as gastroenterologists in the management of complex biliary pathology.

Comparison of Twitter Use of the American Society of Anesthesiologists and the American Association of Nurse Anesthetists.

Twitter has become a powerful tool for dissemination of information. The objective of this study was to evaluate Twitter usage of the American Society of Anesthesiologists (ASA) and the American Association of Nurse Anesthetists (AANA). All tweets from ASA ("@ASALifeline") and AANA ("@aanawebupdates") were collected over a 1-year time period. The content of each tweet was categorized using a rubric. ASA generated more original tweets than AANA. Twitter use was highest in October for ASA and September for AANA. Both societies are actively using Twitter. Future work should evaluate the impact of societal Twitter use.

A metastable subproteome underlies inclusion formation in muscle proteinopathies.

Protein aggregation is a pathological feature of neurodegenerative disorders. We previously demonstrated that protein inclusions in the brain are composed of supersaturated proteins, which are abundant and aggregation-prone, and form a metastable subproteome. It is not yet clear, however, whether this phenomenon is also associated with non-neuronal protein conformational disorders. To respond to this question, we analyzed proteomic datasets from biopsies of patients with genetic and acquired protein aggregate myopathy (PAM) by quantifying the changes in composition, concentration and aggregation propensity of proteins in the fibers containing inclusions and those surrounding them. We found that a metastable subproteome is present in skeletal muscle from healthy patients. The expression of this subproteome escalate as proteomic samples are taken more proximal to the pathologic inclusion, eventually exceeding its solubility limits and aggregating. While most supersaturated proteins decrease or maintain steady abundance across healthy fibers and inclusion-containing fibers, proteins within the metastable subproteome rise in abundance, suggesting that they escape regulation. Taken together, our results show in the context of a human conformational disorder that the supersaturation of a metastable subproteome underlies widespread aggregation and correlates with the histopathological state of the tissue.

Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis.

Urban particulate matter air pollution induces the release of pro-inflammatory cytokines including interleukin-6 (IL-6) from alveolar macrophages, resulting in an increase in thrombosis. Here, we report that metformin provides protection in this murine model. Treatment of mice with metformin or exposure of murine or human alveolar macrophages to metformin prevented the particulate matter-induced generation of complex III mitochondrial reactive oxygen species, which were necessary for the opening of calcium release-activated channels (CRAC) and release of IL-6. Targeted genetic deletion of electron transport or CRAC channels in alveolar macrophages in mice prevented particulate matter-induced acceleration of arterial thrombosis. These findings suggest metformin as a potential therapy to prevent some of the premature deaths attributable to air pollution exposure worldwide.

Rapid vs. delayed infrared responses after ischemia reveal recruitment of different vascular beds.

Continuous infrared imaging revealed transient changes in forearm temperature during arterial occlusion, reperfusion, and recovery in a healthy subject group. Processing the imaging data with the k-means algorithm further revealed reactive vascular sites in the skin with rapid or delayed temperature amplification. The observed temporal and spatial diversity of blood-flow-derived forearm temperature allow consideration of thermal-imaging guided placement of skin sensors to achieve enhanced sensitivity in monitoring of skin hemodynamics.

Surveillance for Clostridium difficile infection in nursing homes.

OBJECTIVES: To define the time of onset of Clostridium difficile infection (CDI) in the community nursing home setting. DESIGN: Retrospective. SETTING: Four community nursing homes. PARTICIPANTS: Residents with incident CDI identified from infection control surveillance records. MEASUREMENTS: Cases were divided into two groups depending on the time of onset of infection: within 30 days of admission after hospitalization or more than 30 days after admission to a nursing home after hospitalization. RESULTS: Of 75 incident CDI cases, 52 (69%) developed within 30 days of admission and 23 (31%) more than 30 days after admission. Of the 52 cases that developed within 30 days, 68% were in residents admitted for subacute care. The mean number of days ± standard deviation to CDI was 10.5 ± 2.5 in those who developed infection within 30 days; 75% of these cases developed within 15 days of admission. CONCLUSIONS: The majority of CDI in the study nursing homes developed within 30 days of admission; this group may be analogous to community-onset, hospital-associated CDI as defined in the Centers for Disease Control and Prevention (CDC) surveillance definitions. Therefore, the proposed CDC surveillance definitions may overestimate the incidence of nursing home-associated CDI.