Predictive Performance Neutrophil-to-Lymphocyte Ratio of Acute Tonsillitis with Deep Neck Space Infection in Adult Patients.

The aim of this study was to examine the neutrophil-to-lymphocyte ratio (NLR) in patients diagnosed with a deep neck infection (DNI) to identify helpful indicators for the initial differential diagnosis. This study was conducted as a single-center, retrospective cohort study that utilized data from the electronic medical records of patients who visited the emergency department in a tertiary university hospital between February 2018 and April 2022. The study enrolled patients aged ≥18 years who were diagnosed with tonsillitis with or without DNI during the study period. The NLR of patients without DNI was 6.1 ± 5.03, and the NLR of patients with acute tonsillitis with DNI was 8.0 ± 5.67, showing significant differences. The rate of admission in the general wards (GWs) and ICUs was significantly higher in patients with DNI, and the length of hospital stay was also significantly longer in patients with DNI. Older age, male, lower body temperature, C-reactive protein, and NLR were significant independent risk factors for DNI in patients with tonsillitis. The cutoff value for predicting DNI in patients with body temperature <37.5 was 3.09. The NLR of patients with tonsillitis, especially those with normal body temperature, can be used to predict their prognosis.

Characteristics of Adolescent Patients Admitted to the Emergency Department due to Attempted Suicide by Poisoning; a Brief Report.

INTRODUCTION: In the background of the increased suicide rate in the second decade of life, analysis of the characteristics of poisoning-related attempted suicide in adolescents and evaluation of the differences from adults may form an important basis for establishing measures to prevent deaths from poisoning. OBJECTIVE: We aimed to investigate the types of toxic substances ingested for attempted suicide by poisoning in adolescents admitted to the emergency department (ED). METHOD: This cross-sectional study retrospectively analyzed and investigated the medical records of patients aged 13 or older, admitted to the ED of a tertiary medical institute over a period of 3 years, for attempted suicide by poisoning. RESULTS: The psychiatric diagnoses among patients in the adolescent group included depression (75.8%), bipolar disorder (12.5%), and panic disorder (12.5%). In terms of the type of drug used for poisoning, antidepressants or anti-psychotics and sleeping pills were the most commonly used in the adolescent (43 subjects, 45.2%) and adult (286 subjects, 37.6%) groups, respectively. CONCLUSION: As there is a higher chance of poisoning by easily accessible drugs, the emergency physician needs to investigate any preceding diagnoses of psychiatric or medical illnesses in the adolescent patients attempting suicide with unknown drugs.

Evidence that gamma-secretase-mediated Notch signaling induces neuronal cell death via the nuclear factor-kappaB-Bcl-2-interacting mediator of cell death pathway in ischemic stroke.

Notch-1 (Notch) is a cell surface receptor that regulates cell-fate decisions in the developing nervous system, and it may also have roles in synaptic plasticity in the adult brain. Binding of its ligands results in the proteolytic cleavage of Notch by the γ-secretase enzyme complex, thereby causing the release of a Notch intracellular domain (NICD) that translocates to the nucleus, in which it regulates transcription. Here we show that activation of Notch modulates ischemic neuronal cell death in vitro and in vivo. Specifically, our findings from the use of Notch-1 siRNA or the overexpression of NICD indicate that Notch activation contributes to cell death. Using modified NICD, we demonstrate an apoptosis-inducing function of NICD in both the nucleus and the cytosol. NICD transfection-induced cell death was reduced by blockade of calcium signaling, caspase activation, and Janus kinase signaling. Inhibition of the Notch-activating enzyme, γ-secretase, protected against ischemic neuronal cell death by targeting an apoptotic protease, cleaved caspase-3, nuclear factor-κB (NF-κB), and the pro-death BH3-only protein, Bcl-2-interacting mediator of cell death (Bim). Treatment of mice with a γ-secretase inhibitor, compound E, reduced infarct size and improved functional outcome in a model of focal ischemic stroke. Furthermore, γ-secretase inhibition reduced NICD, p-p65, and Bim levels in vivo. These findings suggest that Notch signaling endangers neurons after ischemic stroke by modulating the NF-κB, pro-death protein Bim, and caspase pathways.

Contribution of gamma-secretase to calcium-mediated cell death.

Presenilins are the catalytic subunit of the large gamma-secretase complex, that promotes intramembranous proteolysis of the beta-amyloid precursor protein (APP), resulting in the production of beta-amyloid (A beta). Mutant presenilin causes early-onset familial Alzheimer's disease (FAD), is related to abnormal Ca(2+) signaling, and render cells vulnerable to cell death. In the present study, we demonstrated that Ca(2+)-mediated cell death is functionally associated with gamma-secretase activity. We found that gamma-secretase activity was elevated during Ca(2+)-mediated cell death. Using selective gamma-secretase inhibitors, we examined the role of gamma-secretase in cell death triggered by increased intracellular Ca(2+). Indeed, treatment with the selective gamma-secretase inhibitors, compound E, DAPT, or L-685.458 significantly decreased Ca(2+)-triggered cell death with that of the controls, but did not affect staurosporin or tunicamycin-mediated cell death. These results implicate the role of gamma-secretase activity in Ca(2+)-mediated cell death.

Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer's disease.

Beta-secretase (BACE1), an enzyme responsible for the production of amyloid beta-peptide (Abeta), is increased by oxidative stress and is elevated in the brains of patients with sporadic Alzheimer's disease (AD). Here, we show that oxidative stress fails to induce BACE1 expression in presenilin-1 (gamma-secretase)-deficient cells and in normal cells treated with gamma-secretase inhibitors. Oxidative stress-induced beta-secretase activity and sAPPbeta levels were suppressed by gamma-secretase inhibitors. Levels of gamma- and beta-secretase activities were greater in brain tissue samples from AD patients compared to non-demented control subjects, and the elevated BACE1 level in the brains of 3xTgAD mice was reduced by treatment with a gamma-secretase inhibitor. Our findings suggest that gamma-secretase mediates oxidative stress-induced expression of BACE1 resulting in excessive Abeta production in AD.

Characterization of subcellular localization and Ca2+ modulation of calsenilin/DREAM/KChIP3.

Earlier reports found that calsenilin is a transcriptional repressor or a subunit of plasma membrane channel, and indicated that calsenilin was present in the nucleus or plasma membrane. Immunohistochemical and subcellular fractionation analysis, however, revealed that calsenilin/DREAM/KChIP3 was distributed throughout the cytoplasm of SK-N-BE2(C), Jurkat, and HeLa cells. In addition, the expression of calsenilin suppressed the ATP-induced increase in intracellular Ca2+ concentrations. By increase in intracellular calcium concentration, calsenilin was translocated into the nucleus.