The diagnostic value of serum hepcidin in acute appendicitis.

BACKGROUND: Acute appendicitis (AA) is the primary cause of acute abdomen in patients presenting to the emergency department with abdominal pain. Limited studies have explored the relationship between serum hepcidin levels and AA. This study aimed to measure serum hepcidin levels in patients undergoing surgery with a preliminary diagnosis of AA and to assess whether these levels can serve as a biochemical marker for diagnosing AA. METHODS: This study included patients aged 18 or older who presented to the emergency department between April 2018 and May 2019 and underwent surgery with a diagnosis of AA. The cohort comprised 94 patients with surgical pathology results compatible with AA (Group A), 16 patients with results not compatible with AA (Group B), and 42 healthy controls. Serum hepcidin levels were measured from venous blood samples. RESULTS: Mean hepcidin levels were 1750±285 pg/mL in Group A, 1349±381 pg/mL in Group B, and 1066±225 pg/mL in the control group. Statistically significant differences in serum hepcidin levels were observed between Group A and the control group (p<0.05). CONCLUSION: Hepcidin levels were significantly higher in patients with AA compared to both the control group and patients with surgically confirmed non-AA pathology. Therefore, hepcidin may serve as a useful adjunct in diagnosing acute appendicitis.

High-resolution co-seismic fault offsets of the 2023 Türkiye earthquake ruptures using satellite imagery.

On February 6, 2023, southern Türkiye was struck by two large earthquakes at 01:17 UTC (Mw=7.8, Pazarcik, Kahramanmaras) and 10:30 UTC (Mw = 7.6, Elbistan, Kahramanmaras), causing severe damage at the complex junction of the Dead Sea Fault (DSF), the Cyprus Arc and the East Anatolian Fault Zone (EAFZ). The ruptures propagated along several known strands of the southwestern termination of the EAFZ, the main Pazarcik and Karasu valley faults, and the Çardak-Sürgü fault. Here we present the high-resolution mapping of the entire coseismic surface rupture and an estimate of the rupture width, total and on-fault offset, and diffuse deformation obtained a few days to three months after the two mainshocks. The mapping is derived from image correlation of Sentinel-2 optical satellite imagery and validated with offset measurements collected on the ground. We find that the ruptures extend over lengths of 310 km and 140 km for the Mw 7.8 and Mw 7.6 mainshocks, respectively. The maximum offsets reach 7.5 ± 0.8 m and 8.7 ± 0.8 m near the epicenters of the Mw 7.8 and Mw 7.6 events, respectively. We propose a segmentation of the two ruptures based on these observations, and further discuss the location of the potential supershear rupture. The use of optical image correlation, complemented by field investigations along earthquake faults, provides new insights into seismic hazard assessment.

Evaluation of serum uric levels in migraine.

OBJECTIVE: In our study, the aim was to identify the serum uric acid levels, a marker of oxidative stress, according to migraine subtypes (aura/without aura and episodic/chronic migraine). METHOD: The study included 300 migraine patients and 150 healthy controls for a total of 450 individuals. Migraine and subtypes were diagnosed according to International Classification of Headache Disorders-2013 criteria. Patients were evaluated during attendance at the neurology clinic. RESULTS: Our patient group was 77.0% female and disease duration was 9.2 ± 7.2 years. Our control group comprised 77.3% females. The age intervals in the patient and control groups were 36.4 ± 10.4 years and 36.0 ± 8.1 years. There was no statistically significant difference between our control and patient groups in terms of age and gender (p = .937 and p = .655). The serum UA, ferritin, and urea levels in our patient group were found to be significantly low compared to the healthy control group (p < .001). The serum UA levels in the migraine and control groups were 3.7 ± 0.7 and 4.6 ± 0.7 mg/dL, respectively (p < .001). There were no statistically significant differences observed between serum uric acid levels and other blood parameters between aura/without aura and episodic/chronic migraine subtypes (p > .05). CONCLUSION: Our study supports the hypothesis that the oxidative stress marker of serum uric acid levels may be associated with migraine diagnosis, concluding that serum uric acid levels were not significant for migraine subtypes.

Comparison between Hyper-CVAD and PETHEMA ALL-93 in Adult Acute Lymphoblastic Leukemia: A Single-Center Study.

BACKGROUND: Although cure rates in pediatric acute lymphoblastic leukemia (ALL) are quite high with combined chemotherapy regimens, complete response (CR) and long-term survival rates in adults are 80-90 and 30-40%, respectively. Currently, combined chemotherapy regimens, such as Hyper-CVAD and PETHEMA, are used in patients with adult ALL. However, there has been no study comparing the results of Hyper-CVAD and PETHEMA ALL-93. METHODS: In this retrospective single-center study, we evaluated the results of Hyper-CVAD and PETHEMA ALL-93 in 51 ALL patients treated between September 2008 and March 2017 at the Department of Hematology, Faculty of Medicine, Karadeniz Technical University. RESULTS: Thirty-eight patients were treated with Hyper-CVAD and 13 with PETHEMA ALL-93. CR was obtained in 90 and 100% of patients, respectively. Survival estimates were comparable between Hyper-CVAD and PE-THEMA ALL-93, with a median overall survival (OS) and a median disease-free survival (DFS) of 17.5 and 12.1 months, respectively, for Hyper-CVAD and of 18.6 and 12.9 months, respectively, for PETHEMA ALL-93. The 2-year OS rates for Hyper-CVAD and PETHEMA ALL-93 were 30 and 40%, respectively, and the 2-year DFS rates were 28 and 44%, respectively. PETHEMA ALL-93 resulted in more hepatotoxicity, hypofibrinogenemia, aspergillus infection, and skin rash than Hyper-CVAD. CONCLUSIONS: Although Hyper-CVAD and PE-THEMA ALL-93 showed similar effects, Hyper-CVAD was tolerated better. Age and comorbidities should be taken into account before a chemotherapy regimen is determined for patients with ALL.

Cell-to-cell variability analysis dissects the plasticity of signaling of common γ chain cytokines in T cells.

Natural variability in the abundance of signaling regulators can lead to divergence in cell fate, even within genetically identical cells that share a common differentiation state. We introduce cell-to-cell variability analysis (CCVA), an experimental and computational methodology that quantifies the correlation between variability in signaling regulator abundance and variation in the sensitivity of cells to stimuli. With CCVA, we investigated the unexpected effects of the interleukin 2 (IL-2) receptor α chain (IL-2Rα) on the sensitivity of primary mouse T lymphocytes to cytokines that signal through receptors that have the common γ chain (γ(c)). Our work showed that increased IL-2Rα abundance decreased the concentration of IL-2 required for a half-maximal activation (EC(50)) of the downstream effector signal transducer and activator of transcription 5 (STAT5), but reduced the responsiveness to IL-7 or IL-15, without affecting the EC(50) values of other γ(c) cytokines. To investigate the mechanism of the effect of IL-2Rα on γ(c) cytokine signaling, we introduced a Bayesian-inference computational framework that models the formation of receptor signaling complexes with data from previous biophysical measurements. With this framework, we found that a model in which IL-2Rα drives γ(c) depletion through the assembly of functional IL-2R complexes was consistent with both the CCVA data and experimental measurements. The combination of CCVA and computational modeling produced quantitative understanding of the crosstalk between γ(c) cytokine receptor signaling in T lymphocytes.

Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity.

The polarization of adipose tissue-resident macrophages toward the alternatively activated, anti-inflammatory M2 phenotype is believed to improve insulin sensitivity. However, the mechanisms controlling tissue macrophage activation remain unclear. Here we show that adipocytes are a source of Th2 cytokines, including IL-13 and to a lesser extent IL-4, which induce macrophage PPARdelta/beta (Ppard/b) expression through a STAT6 binding site on its promoter to activate alternative activation. Coculture studies indicate that Ppard ablation renders macrophages incapable of transition to the M2 phenotype, which in turns causes inflammation and metabolic derangement in adipocytes. Remarkably, a similar regulatory mechanism by hepatocyte-derived Th2 cytokines and macrophage PPARdelta is found to control hepatic lipid metabolism. The physiological relevance of this paracrine pathway is demonstrated in myeloid-specific PPARdelta(-/-) mice, which develop insulin resistance and show increased adipocyte lipolysis and severe hepatosteatosis. These findings provide a molecular basis to modulate tissue-resident macrophage activation and insulin sensitivity.