Sepsis-associated brain injury (SABI) is characterized by an acute deterioration of mental status resulting in cognitive impairment and acquisition of new and persistent functional limitations in ...sepsis survivors. Previously, we reported that septic mice had evidence of axonal injury, robust microglial activation, and cytotoxic edema in the cerebral cortex, thalamus, and hippocampus in the absence of blood-brain barrier disruption. A key conceptual advance in the field was identification of sulfonylurea receptor 1 (SUR1), a member of the adenosine triphosphate (ATP)-binding cassette protein superfamily, that associates with the transient receptor potential melastatin 4 (TRPM4) cation channel to play a crucial role in cerebral edema development. Therefore, we hypothesized that knockout (KO) of Abcc8 (Sur1 gene) is associated with a decrease in microglial activation, cerebral edema, and improved neurobehavioral outcomes in a murine cecal ligation and puncture (CLP) model of sepsis. Sepsis was induced in 4-6-week-old Abcc8 KO and wild-type (WT) littermate control male mice by CLP. We used immunohistochemistry to define neuropathology and microglial activation along with parallel studies using magnetic resonance imaging, focusing on cerebral edema on days 1 and 4 after CLP. Abcc8 KO mice exhibited a decrease in axonal injury and cytotoxic edema vs. WT on day 1. Abcc8 KO mice also had decreased microglial activation in the cerebral cortex vs. WT. These findings were associated with improved spatial memory on days 7-8 after CLP. Our study challenges a key concept in sepsis and suggests that brain injury may not occur merely as an extension of systemic inflammation. We advance the field further and demonstrate that deletion of the SUR1 gene ameliorates CNS pathobiology in sepsis including edema, axonal injury, neuroinflammation, and behavioral deficits. Benefits conferred by Abcc8 KO in the murine CLP model warrant studies of pharmacological Abcc8 inhibition as a new potential therapeutic strategy for SABI.
With the increasing demand of natural resources and its existence at higher depth, rock mechanics is facing a completely new challenge of rock mass behavior at higher temperature. The majority of ...rock masses for instance found in nuclear waste burial sites, geothermal energy extraction, enhanced and natural geothermal system and underground development of deep mine, oil and gas storage cavern encounters high temperatures and therefore rock strength and deformation characteristics under high temperature need to be studied in detail. During the last few years, some investigations have been carried out in this field.
Air-atomized spray cooling, where compressed air atomizes water into fine droplets, is an efficient alternative to conventional cooling techniques. The present work deals with the air-atomized spray ...cooling of a 6 mm thick stainless steel plate having an initial surface temperature of 900 °C, using surfactant Tween 20 and ethanol additives. The main difficulty in achieving a high cooling rate at elevated surface temperatures is the Leidenfrost phenomenon. The metallurgical properties of steel are highly affected by the run-out table cooling rate between the temperature range of 900–600 °C. Another important cooling region, particularly to achieve the high strength martensite microstructure in steel, is 900 °C–200 °C. Therefore, in this study, the heat transfer studies have been done over those temperature regions. The physical properties of the coolant mixture were measured to understand the heat transfer enhancement mechanism. The results show that increasing the ethanol fraction in pure water (with or without surfactant) enhances the critical heat flux, heat transfer coefficient and cooling rate of a hot surface in the nucleate and transition boiling regimes. A maximum cooling rate of 183 °C/s has been obtained with the ethanol–water mixture; whereas ethanol–water–surfactant mixture gives a cooling rate of 235 °C/s, both of which lie in ‘ultrafast cooling’ regime.
•Air-atomized water spray cooling of a very high temperature surface was investigated.•Surfactant and ethanol additives promoted the transition and nucleate boiling heat transfer rates.•Critical heat flux value increased by using additives in pure water coolant.•Additives in coolant enhanced the cooling rate up to 235 °C/s for ROT application.•The obtained cooling rates were found to be in the higher range of an UFC.
Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic ...stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.
Introduction Some studies advocate a laparoscopic extralevator abdominoperineal excision (l-ELAPE) approach for low rectal cancer. The da Vinci™ robot (r-ELAPE) technique has potential to overcome ...some limitations of l-ELAPE, such as reduction of the learning curve and more precise tissue handling. It is unknown whether this approach results in improved surgical or quality of life outcomes compared with l-ELAPE. This study aimed to address this issue. Methods Consecutive patients having undergone either robotic or laparoscopic ELAPE for adenocarcinoma were studied. All operations were performed by two surgeons experienced in laparoscopic and recently introduced robotic surgery. Surgical outcomes were determined by postoperative histology and short-term complications. Quality of life was prospectively assessed using the European Organisation for Research and Treatment of Cancer QLC-CR30 and QLC-CR29 questionnaires. Results A total of 22 patients (11 r-ELAPE) with a median follow-up of 13 months (8 months robotic; 22 months laparoscopic) were studied. The groups were similarly matched for age, gender, American Society of Anesthesiologists status, preoperative chemoradiotherapy and tumour height. All had R0 resection. There was no significant difference in short-term surgical outcomes between groups. There was no significant difference in mean global health scores between the two groups (74 ± 14 r-ELAPE vs. 73 ± 10 l-ELAPE). The r-ELAPE group had a lower mean impotence score compared with the I-ELAPE group (55.5 ± 40 vs. 72.2 ± 44), although this was not statistically significant. Conclusions The newly introduced r-ELAPE was non-inferior to l-ELAPE in either patient quality of life or surgical outcomes. Robotic surgery could be particularly beneficial in the technically challenging area of low rectal cancer surgery with a shorter learning curve than laparoscopy.
•Air-atomized spray cooling of hot 900°C stainless steel plate studied experimentally.•Water with high impingement density is used to get ultrafast cooling rate >140°C/s.•Cooling rate is enhanced by ...addition of SDS, CTAB and Tween 20 surfactants to water.•Surfactant concentration and type of surfactant have strong influence on heat transfer rate.•Surfactant of less foam formability has high heat removal capacity.
Ultrafast cooling of a 6mm thick hot stainless steel plate (AISI 304) has been achieved by high flow conditions of air and water, which is needed at the runout table of a hot strip mill to develop advanced high strength steels. The present study primarily focuses on the effect of adding different types of surfactants at various concentration levels to air atomized water spray for enhancement of ultrafast cooling rate. The anionic, cationic and non-ionic surfactants used have been characterized by measuring their surface tension, contact angle and viscosity. The surfactant enhanced heat transfer experiments have been conducted with a full cone atomizer at a fixed nozzle to surface distance using constant air and water flow rates optimized earlier. The initial surface temperature of the test plate has been maintained at 900°C in each case. The experimental measurements have been applied to a commercial inverse heat conduction solver (INTEMP) to estimate local surface heat flux as well as surface temperature histories. The concentration of all the surfactants has been optimized based on the highest cooling rate. Depending on their spreadability, wetting characteristics and ability to foam formation, the cationic and non-ionic surfactants are found to produce better cooling effects than the anionic surfactant. These enhanced ultrafast cooling rates can be useful to produce advanced high strength steels in the steel industries.
Summary
Two different Toll‐like receptors (TLRs) have been shown to play a role in host responses to Leishmania infection. TLR‐2 is involved in parasite survival in macrophages upon activation by ...lipophosphoglycan (LPG), a virulence factor expressed by Leishmania. In contrast, activation of TLR‐9 has been shown to promote a host‐protective response. However, whether there is a relationship between the interaction of LPG and TLR‐2, on one hand, with the effect of TLR‐9, on the other hand, remains unknown. In this study, we report that in‐vitro infection of macrophages with a L. major parasite with high expression levels of LPG results in decreased TLR‐9 expression compared to infection with a L. major parasite with lower expression levels of LPG. Addition of anti‐LPG as well as anti‐TLR‐2 antibodies prevents this reduction of TLR‐9 expression. Also, the addition of purified LPG to macrophages results in a decrease of TLR‐9 expression, which is shown to be mediated by transforming growth factor (TGF)‐β and interleukin (IL)‐10. Finally, in‐vitro treatment of macrophages with anti‐LPG and/or anti‐TLR‐2 antibodies before infection reduces the number of amastigotes in macrophages and co‐treatment of mice with anti‐TLR‐2 antibodies and cytosine–phosphate–guanosine (CpG) reduces footpad swelling and parasite load in the draining lymph nodes, accompanied by an interferon (IFN)‐γ‐predominant T cell response. Thus, for the first time, we show how interactions between LPG and TLR‐2 reduce anti‐leishmanial responses via cytokine‐mediated decrease of TLR‐9 expression.
Background
Optimal definitive treatment timing for patients with aneurysmal subarachnoid hemorrhage (aSAH) remains controversial. We compared outcomes for aSAH patients with ultra-early treatment ...versus later treatment at a single large center.
Method
Patients who received definitive open surgical or endovascular treatment for aSAH between January 1, 2014, and July 31, 2019, were included. Ultra-early treatment was defined as occurring within 24 h from aneurysm rupture. The primary outcome was poor neurologic outcome (modified Rankin Scale score > 2). Propensity adjustment was performed for age, sex, Charlson Comorbidity Index, Hunt and Hess grade, Fisher grade, aneurysm treatment type, aneurysm type, size, and anterior location.
Results
Of the 1013 patients (mean SD age, 56 14 years; 702 69% women, 311 31% men) included, 94 (9%) had ultra-early treatment. Compared with the non-ultra-early cohort, the ultra-early treatment cohort had a significantly lower percentage of saccular aneurysms (53 of 94 56% vs 746 of 919 81%,
P
<0 .001), greater frequency of open surgical treatment (72 of 94 77% vs 523 of 919 57%,
P
<0 .001), and greater percentage of men (38 of 94 40% vs 273 of 919 30%,
P
= .04). After adjustment, ultra-early treatment was not associated with neurologic outcome in those with at least 180-day follow-up (OR = 0.86), the occurrence of delayed cerebral ischemia (OR = 0.87), or length of stay (exp(β), 0.13) (
P
≥ 0.60).
Conclusions
In a large, single-center cohort of aSAH patients, ultra-early treatment was not associated with better neurologic outcome, fewer cases of delayed cerebral ischemia, or shorter length of stay.
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