The role of orexin in fatigue and sleep quality in patients with primary Sjögren's syndrome.

BACKGROUND: Sleep disorders and fatigue are prevalent symptoms affecting primary Sjögren's syndrome (pSS) patients. This study aimed to assess the sleep quality of pSS patients as well as its relationship to fatigue and orexin level. METHODS: This is a cross-sectional study evaluating fatigue in pSS using the Fatigue Severity Scale (FSS). Sleep quality was evaluated using the Pittsburg Sleep Quality Index (PSQI). The European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) were calculated. RESULTS: Forty-one patients met the sample criteria and were involved in the final report. They were all females, with a mean (± SD) age and median disease duration of 40.87 ± 10.84 and 36 (6-180) months, respectively. The mean ESSDAI was 0.92 ± 1.3, while the mean ESSPRI was 5.8 ± 2.13. Based on the FSS, 32 (78.04%) patients had a positive test with a mean score of 5.07 ± 1.54. The total PSQI score showed that 60.97% had poor sleep, and the orexin level was lower in patients with pSS than in healthy controls. There was no correlation between orexin level and the presence of fatigue nor the PSQI score. CONCLUSION: In conclusion, serum orexin levels were lower in patients with pSS than healthy controls, It could be related to impairments in sleep and fatigue in patients with pSS.

Adrenomedullin predicts high risk and culture positivity in children with solid tumors suffering from neutropenic fever.

AIM OF STUDY: Neutropenic fever is a source of morbidity and mortality in children with cancer. It is not possible to detect the causative agent in cultures in most cases; the research for a marker that can show the severity of the disease is ongoing. We evaluated the role of adrenomedullin (ADM) at predicting prognosis on patients with febrile neutropenia, which has been proven to be a good prognostic marker for diseases with high morbidity and mortality, such as heart failure, ischemic ventricular dysfunction, sepsis, and systemic inflammatory response syndrome. MATERIALS AND METHODS: We recorded the 36 febrile episodes of 14 children receiving chemotherapy due to solid tumors. There were 10 events with unknown origin in the low-risk group, while in the high-risk group, there were 17 events with unknown origin, 8 events with microbiological origin and 1 event with clinically proven infection. Cultures were positive only in the high-risk group. However, the changes of ADM levels through time periods (first, second, third, and seventh days) were not significant. RESULTS: The first-day plasma ADM levels significantly predicted the presence of culture positivity (AUC 0.628, 95% CI 0.40-0.85, p = 0.303) and high-risk patients with neutropenic fever (AUC 0.76, 95% CI 0.56-0.97, p = 0.016). CONCLUSION: Our study showed that increased plasma ADM was correlated with high-risk neutropenic fever and culture positivity. The ADM levels in the high-risk group were clearly high at the diagnosis and continued to the end of the treatment.

The relationship between the VEGF/sVEGFR-1 ratio and threatened abortion.

PURPOSE: The aim of this study was to evaluate the levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sVEGFR-1) and placenta growth factor (PlGF) and VEGF/SVEGFR-1 ratio in pregnant women with threatened abortion (TA) compared to uncomplicated pregnancies at the same gestational week. METHODS: Thirty-three pregnant women with TA and thirty-three pregnant women with uncomplicated pregnancies were included in this case-control study. The level of VEGF, sVEGFR-1, and PIGF was analyzed by enzyme-linked immunosorbent assay (ELISA). The primary purpose of this study was to compare the VEGF, sVEGFR- 1, and PlGF levels and VEGF/sVEGFR-1 ratios in pregnant women with TA and pregnant women with uncomplicated pregnancies. The secondary purpose of this study was to evaluate the correlation between serum levels of these markers and gestational age. RESULTS: The serum levels of the sVEGFR-1 [0.60 (0.21-1.68) vs. 0.24 (0.09-0.57) ng/ml], VEGF [39.10 (6.57-163.56) vs. 5.24 (0.84-15.08) ng/ml] and VEGF/SVEGFR-1 ratio [68.64 (6.45-550.48) vs 24.12 (2.63-72.63)] were significantly elevated in women with TA (respectively, p: 0.001, p: 0.001, p: 0.001). However, PlGF did not elevate in women with TA [20.80 (3.13-93.11) vs 20.16 (1.22-49.91) ng/ml] (p: 0.473). CONCLUSION: These findings support the hypothesis that increased levels of the VEGF and sVEGFR-1 and VEGF/SVEGFR-1 ratio may be associated with the pathogenesis of TA.

The evaluation of inflammatory markers in umbilical cord blood.

We have read with great interest the article by Lausten-Thomsen et al. entitled "Inflammatory Markers in Umbilical Cord Blood from Small-For-Gestational-Age Newborns" in which they report Interleukin 6 (IL-6), Tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) levels in umbilical cord blood from small-for-gestational-age (SGA) and healthy newborns. In this regard, we would like to make some additions to paper in respect to interpretations of biochemical markers. Normal CRP concentration in healthy human serum is usually lower than 10 mg/L, slightly increasing with aging. Acute inflammatory response causes release of IL-6 and other cytokines that trigger the synthesis of CRP by the liver. In this article, IL-6 levels reported as elevated but CRP levels have remained in normal range. In this situation, increasing in IL-6 levels should be approached suspiciously. Although decreased TNF-α level was compatible with IL-6 levels, increased IL-6 levels did not cause CRP elevation in this study.

A challenging issue in COVID-19 infection: The relationship between PA1-1 and TAFI levels in patients with coagulation disorder: A retrospective and observational study.

COVID-19 disrupts the balance between coagulation and fibrinolysis. Especially in the clinical course of serious disease, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), and tissue plasminogen activator levels increase in association with hypercoagulable state and hypofibrinolysis. This explains the increased incidence of thrombosis seen in COVID-19 infection. In this study, we aimed to examine the changes in PAI-1 and TAFI levels of COVID-19 patients. Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital-Ankara Turkey, between April 1 and May 7, 2021. Patients who were diagnosed with COVID-19 were included in this retrospective study. TAFI and PAI-1 levels were analyzed from the samples that had been stored at -80 °C formerly. One hundred thirty-five patients diagnosed with COVID-19 and followed up in the service or intensive care unit were included in the study. Thirty-four (25.2%) patients required follow-up in the intensive care unit. Mortality rate was 10.4%, the coagulation tests of these patients were also compared. PA1-1 levels were found to be statistically significantly higher in intensive care unit patients (median: 133 pg/mL vs 31 pg/mL; P < .001), and there was no significant difference in TAFI levels (median:7.31 ng/mL vs 9.80 ng/mL; P = .171) between the 2 groups. TAFI levels were found to be higher in patients who died. In COVID-19 infection, as the severity of the disease increases, the coagulation balance deteriorates and eventually a hypercoagulable state occurs with an increase in PAI-1 and TAFI levels. Markers such as PAI and TAFI can be illuminating in further studies in determining prognosis and mortality and developing new treatment options.

Effects of various cryoprotectants on bull sperm quality, DNA integrity and oxidative stress parameters.

The objectives of this study was to compare the effects of type and concentration of cryoprotectants glycerol (G), ethylene glycol (EG) and dimethyl sulfoxide (DMSO) on the plasma membrane and DNA integrity as well as antioxidant activity of cryopreserved Eastern Anatolian red bull sperm. Ejaculates were collected from the three bulls using an artificial vagina twice a week. The ejaculates were pooled to increase the semen volume for replication and to eliminate variability among the evaluated samples. The pooled ejaculates were also split into seven equal experimental groups and diluted with the modified base extender to a final spermatozoa concentration of 15×10(6)/ml. The extended samples were cooled slowly to 4°C and equilibrated for 4h. They were then loaded into 0.25ml French straws and frozen using a digital freezing machine at 3 programmed rates: -3°C/min from +4°C to -10°C, -40°C/min from -10°C to -100°C, and -20°C/min from -100°C to -140°C. Thereafter, the straws were plunged into liquid nitrogen at -196°C. Frozen straws were thawed individually at 37°C for 30s in a water bath to analyse progressive motility and sperm motion characteristics as well as membrane integrity using hypo-osmotic swelling test. Biochemical assays were performed in a spectrophotometer using commercial kits. DNA damage was evaluated by Comet Assay using Image Analysis System. 6% G exhibited the greatest percentages of CASA (43.7±2.92%) and progressive (26.4±2.64%) motilities when compared to the other groups (P<0.001). 6% G and 6% EG showed the greatest values of preserved membrane integrity (P<0.001). 6% DMSO and 3% EG + 3% DMSO resulted in greater chromatin damage than the other groups (P<0.001). The antioxidant activities of GPx, GSH, and CAT as well as the total antioxidant activity were affected by the type of cryoprotectant; notably, 2% G+2% EG+2% DMSO yielded the lowest activities when compared to the other groups (P<0.001). In conclusion, no advantages were found in using EG or DMSO to replace G in bull sperm cryopreservation. Freezing with cryoprotectant 6% G yielded the best post-thaw sperm characteristics for Eastern Anatolian Red bull spermatozoa.

The effects of N-acetylcysteine and ozone therapy on oxidative stress and inflammation in acetaminophen-induced nephrotoxicity model.

INTRODUCTION: Acetaminophen (APAP) is an analgesic and antipyretic agent. In overdoses, it is associated with nephrotoxicity. We examined the potential protective effects of N-acetylcysteine (NAC) and NAC + ozone therapy (OT) combination against APAP-induced nephrotoxicity. MATERIALS AND METHODS: Thirty-two male Sprague-Dawley rats were divided into four groups: sham, control (APAP), NAC, and NAC + OT. In the APAP, NAC, and NAC + OT groups, kidney injury was induced by oral administration of 1 g/kg APAP. The NAC group received NAC (100 mg/kg/day). NAC + OT group received NAC (100 mg/kg/day) and ozone/oxygen mixture (0.7 mg/kg/day) intraperitoneally for 5 days immediately after APAP administration. All animals were killed at 5 days after APAP administration. Renal tissues and blood samples were obtained for biochemical and histopathological analyses. Neopterin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10 levels were measured in sera. Malondialdehyde (MDA) levels and glutathione peroxidase (GPx) activities were determined in renal homogenates. RESULTS: NAC and NAC + OT significantly decreased MDA and TNF-α levels and increased IL-10 levels and GPx activities. Serum neopterin and IL-6 levels were not different among all groups. APAP administration caused tubular necrosis in the kidney. The degrees of renal necrosis of the APAP group were higher than the other groups. Renal injury in rats treated with combination of NAC and OT were found to be significantly less than the other groups. CONCLUSIONS: Our results showed that NAC and OT prevented renal injury in rats and reduced inflammation. These findings suggest that combination of NAC and OT might improve renal damages because of both oxidative stress and inflammation.

Lipoprotein-associated phospholipase A2 and carotid intima-media thickness in primary Sjögren syndrome.

Objectives: This study aims to evaluate serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and carotid intima-media thickness in primary Sjögren syndrome (pSS) as an indicator of atherosclerosis. Patients and methods: Between July 2019 and July 2020, a total of 33 female pSS patients (mean age: 44.5±11.2 years; range, 23 to 60 years) and 37 female age- and sex-matched healthy individuals (mean age: 40.9±7.2 years; range, 25 to 54 years) were included. Carotid intima-media thickness and serum Lp-PLA2 levels were measured in the patient and control groups. Results: The patients had a higher median serum Lp-PLA2 of 560 (range, 108 to 1,222) ng/mL vs. 328 (range, 0 to 1,280) ng/mL in the controls (p=0.024) and a similar mean intima-media thickness of carotid artery (0.64±0.14 mm vs. 0.62±0.15 mm, respectively; p=0.595). Serum Lp-PLA2 was positively correlated with platelet count (r=0.411, p=0.018) and negatively correlated with erythrocyte sedimentation rate (r=-0.409, p=0.018). The mean value of carotid intima-media thickness was positively correlated with disease duration (r=0.316, p=0.074) and was negatively correlated with the level of leucocyte (r=-0.458, p=0.007). Conclusion: Our study suggests that the patients of pSS have a potential risk of atherosclerotic cardiovascular disease, independent of traditional cardiovascular risk factors and disease severity.