T-cell receptor signaling modulated by the co-receptors: Potential targets for stroke treatment.

Stroke is a severe and life-threatening disease, necessitating more research on new treatment strategies. Infiltrated T lymphocytes, an essential adaptive immune cell with extensive effector function, are crucially involved in post-stroke inflammation. Immediately after the initiation of the innate immune response triggered by microglia/macrophages, the adaptive immune response associated with T lymphocytes also participates in the complex pathophysiology of stroke and partially informs the outcome of stroke. Preclinical and clinical studies have revealed the conflicting roles of T cells in post-stroke inflammation and as potential therapeutic targets. Therefore, exploring the mechanisms that underlie the adaptive immune response associated with T lymphocytes in stroke is essential. The T-cell receptor (TCR) and its downstream signaling regulate T lymphocyte differentiation and activation. This review comprehensively summarizes the various molecules that regulate TCR signaling and the T-cell response. It covers both the co-stimulatory and co-inhibitory molecules and their roles in stroke. Because immunoregulatory therapies targeting TCR and its mediators have achieved great success in some proliferative diseases, this article also summarizes the advances in therapeutic strategies related to TCR signaling in lymphocytes after stroke, which can facilitate translation.

Nanobrick wall multilayer thin films grown faster and stronger using electrophoretic deposition.

In an effort to speed up the layer-by-layer (LbL) deposition technique, electrophoretic deposition (EPD) is employed with weak polyelectrolytes and clay nanoplatelets. The introduction of an electric field results in nearly an order of magnitude increase in thickness relative to conventional LbL deposition for a given number of deposited layers. A higher clay concentration also results with the EPD-LbL process, which produces higher modulus and strength with fewer deposited layers. A 20 quadlayer (QL) assembly of linear polyethyleneimine (LPEI)/poly(acrylic acid)/LPEI/clay has an elastic modulus of 45 GPa, tensile strength of 70 MPa, and thickness of 4.4 µm. Traditional LbL requires 40 QL to achieve the same thickness, with lower modulus and strength. This study reveals how these films grow and maintain a highly ordered nanobrick wall structure that is commonly associated with LbL deposition. Fewer layers required to achieve improved properties will open up many new opportunities for this multifunctional thin film deposition technique.

Premorbid Use of Beta-Blockers or Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Patients with Acute Ischemic Stroke.

This study was designed to investigate the impact of the preexisting use of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) on the cellular immune response in peripheral blood and the clinical outcomes of patients with acute ischemic stroke. We retrospectively collected clinical data from a cohort of 69 patients with premorbid beta-blockers and 56 patients with premorbid ACEIs/ARBs. Additionally, we selected a cohort of 107 patients with acute ischemic stroke to be the control of the same age and sex. We analyzed cellular immune parameters in peripheral blood 1 day after the appearance of symptoms, including the frequencies of circulating white blood cell subpopulations, the neutrophil-to-lymphocyte ratio (NLR), and the lymphocyte-to-monocyte ratio (LMR). We found that the count of lymphocytes and the lymphocyte-to-monocyte ratio were significantly higher in the peripheral blood of patients treated with beta-blockers before stroke than in matched controls. However, the premorbid use of ACEIs/ARBs did not considerably impact the circulating immune parameters listed above in patients with acute ischemic stroke. Furthermore, we found that premorbid use of beta-blockers or ACEIs/ARBs did not significantly change functional outcomes in patients 3 months after the onset of stroke. These results suggest that premorbid use of beta-blockers, but not ACEIs/ARBs, reversed lymphopenia associated with acute ischemic stroke. As cellular immune changes in peripheral blood could be an independent predictor of stroke prognosis, more large-scale studies are warranted to further verify the impact of premorbid use of beta-blockers or ACEIs/ARBs on the prognosis of patients with ischemic stroke. Our research is beneficial to understanding the mechanism of the systemic immune response induced by stroke and has the potential for a therapeutic strategy in stroke interventions and treatment.

Bee swarmings in children.

UNLABELLED: Africanized honeybees (Apis mellifera scutellata) are now found in the southern and southwestern United States. Swarmings can result in hundreds to thousands of stings delivering a venom load capable of producing multisystem organ failure and death. The literature on mass envenomations is scarce, being limited to case reports and case series. There are no prospective studies on mass envenomations in children. METHODS: All patients were admitted to our toxicology service, and all stingers were counted. Laboratory data and clinical assessments were obtained at baseline, 8, and 16 hours after presentation. RESULTS: Nineteen patients with a median age of 3.6 years and a median of 2.64 stings per kilogram (range, 1-4.5) were enrolled. Fifteen children had vomiting. Only a mild increase in creatine kinase was seen. None developed coagulopathy or renal insufficiency. CONCLUSION: Envenomations of up to 4.5 stings per kilogram resulted in only mild systemic illness. Vomiting does not portend involvement of other organ systems.

Postcollection rise in methemoglobin level in frozen blood specimens.

A patient with nonspecific complaints had four previous venous blood samples showing elevated methemoglobin fractions of 15.6-20.1%. Cooximetry on a fresh specimen revealed a methemoglobin fraction of 0.8%, while that reported by the original laboratory on the simultaneously collected specimen was 14.9%. The laboratory assayed the specimen after holding it in frozen storage. Venous blood from a healthy volunteer was assayed by cooximetry after storage under conditions of room temperature (22-24 degrees C), refrigeration (1-4 degrees C), and freezing (-14 to -12 degrees C). Methemoglobin level in frozen-thawed specimens rose over time from 1.8% (0.29 g/dL) at 6 hour to 10.9% (1.71 g/dL) after 6 days. With the exception of a single specimen stored in an EDTA-containing tube at room temperature for 6 days, methemoglobin in nonfrozen specimens never exceeded 0.8% (0.12 g/dL).

Acute propylene glycol ingestion.

BACKGROUND: We describe a case of acute propylene glycol toxicity following ingestion of ethanol and propylene glycol-containing antifreeze in which blood lactate, serum propylene glycol, ethanol, and CO2 concentrations were serially measured. CASE REPORT: A 61-year-old man was hospitalized after acute ingestion of ethanol and automotive antifreeze. His clinical presentation and course were essentially unremarkable. Initial lab tests revealed serum ethanol concentration, 167 mg/dL, normal serum electrolytes and osmol gap, 120 mOsm/kg. Intravenous 10% ethanol infusion was begun for suspected ethylene glycol toxicity and discontinued at approximately 17 hours post-ingestion. Toxicological analysis of urine was positive for ethanol and propylene glycol, and negative for ethylene glycol, methanol, and isopropanol. Blood lactate was mildly elevated and serum CO2 concentration was normal. Gas chromatographic analysis of serial serum specimens for propylene glycol concentration revealed a maximum value of 470 mg/dL at 7 hours and a nonlinear decline to below detection limit (3 mg/dL) at 57 hours after antifreeze ingestion. The patient was discharged on hospital day 2. CONCLUSION: The propylene glycol elimination pattern, absence of significant acid-base disturbance, and minimal lactate elevation in this case are consistent with ethanol-related inhibition of propylene glycol metabolism. The effect of ethanol on clinical outcome after acute propylene glycol intoxication remains uncertain.