The role of thiol-disulfide homeostasis and ischemia-modified albumin in osteosarcopenia.

BACKGROUND: Oxidative stress results from an imbalance between the induction of reactive oxygen species and the ability of cells to metabolize them. Numerous markers can be used to assess the level of oxidative stress. Thiol-disulfide homeostasis (TDH) and ischemia-modified albumin (IMA) are some of them. The aim of this study is to investigate the role of TDH and IMA, which are indicators of oxidative stress, in older patients with osteosarcopenia (OS). METHODS: The study was conducted cross-sectionally in a geriatrics outpatient clinic. Patients who applied to the outpatient clinic for three months were included in the study. Patients with acute infection, delirium, malignancy, severe liver, heart or kidney dysfunction and who did not give their consent for the study were excluded from the study. The study was conducted with 136 patients. Sarcopenia was diagnosed according to muscle ultrasonography (USG) and handgrip strength (HGS) results. Osteopenia/osteoporosis was diagnosed according to bone mineral densitometry (BMD) results. The combination of osteopenia/osteoporosis and sarcopenia was accepted as OS. RESULTS: Native thiol, total thiol value and nativethiol /totalthiol*100 values were significantly lower in the group with OS (respectively; value = 265 ± 53.8 standard deviation (SD) µmol/L, p = ≤ 0.001; value = 295.33 ± 55.77 SD µmol/L, p = 0.001; value = 90.06 (2.8) interquartile ranges (IQR), p = 0.033). Disulfide/native thiol*100 and disulfide/total thiol*100 values were significantly higher in the group with OS (respectively; value = 5.5 (1.7) IQR, p = 0.033; value = 4.97 (1.4) IQR, p = 0.034). CONCLUSION: In our study, the role of oxidative stress in OS was demonstrated by using TDH as an oxidative stress parameter.

Serum netrin-1 levels are high in Rheumatoid arthritis associated interstitial lung disease.

BACKGROUND: Recent data show that netrin-1 has a role in development of pulmonary fibrosis. This study was aimed to investigate serum netrin-1 level and its relation to interstitial lung disease(ILD) in patients with rheumatoid arthritis (RA). METHOD: 42 RA patients with RA-ILD, 58 RA patients without RA-ILD (RA non-ILD group), and 61 healthy volunteers were included in this study. The modified DAS28-ESR score was used to calculate disease activity in RA patients. Using the quantitative immunoassay method, Serum netrin-1 levels were measured with an ELISA kit (Catalog number: E-EL-H2328; lab science, lot number: GZWTKZ5SWK, Texas, USA). RESULTS: The median value of netrin-1 was found to be significantly higher in the RA-ILD group (82.9 [59.9-124]) compared to both the RA non-ILD group(52.9 [49.5-73.1])(B = -0.006, OR = 0.994, CI 95 %=0.989-0.999, P = 0.018) and the control group(53.5 [49.5-87.5]) (B: -0.005, OR: 0.994, CI 95 %: 0.990-0.999, p: 0.022). A cut-off value of 61.78 for netrin-1 was found to have a sensitivity of 73.8 % and a specificity of 69 % for the diagnosis of RA-ILD (AUC [95 %Cl] = 0.771 [0.679-0.862], p < 0.0001).It was found that high serum netrin-1 level was strongly associated with the RA-usual interstitial pneumonia(UIP) pattern and poorly related to the RA-nonspecific interstitial pneumonia(NSIP) pattern compared to the RA non-ILD group. CONCLUSIONS: Netrin-1 is elevated in the serum of patients with RA-ILD, especially in the UIP pattern. Netrin-1 may be a potential candidate for predicting the development of RA-ILD that should be investigated in the pathophysiological and therapeutic fields..

Relationship between pattern reversal visual evoked potential P100 wave latency and dysfunctional HDL in patients with multiple sclerosis subjected to an optic neuritis attack: A case-control study.

Optic neuritis frequently occurs during the clinical course of multiple sclerosis (MS). In this condition, demyelination of the optic nerve occurs, which electrophysiologically causes a delay in P100 wave latency. Sensitive cholesterol homeostasis is critical for the formation of the myelin sheath and for myelin to become functionally mature. High-density lipoprotein (HDL) becomes dysfunctional under oxidative stress and plays an important role in the pathogenesis of MS. In this study, HDL levels of MS patients suffering from optic neuritis were compared with those of healthy individuals, and the relationship between pattern reversal visual evoked potential (PRVEP) P100 wave latency and HDL levels in patients with optic neuritis attacks was analyzed. PRVEP studies were performed in patients with MS who had an episode of optic neuritis, and P100 wave latencies were measured. Peripheral blood samples were collected from healthy participants and patients. Lipid levels and myeloperoxidase (MPO) and paraoxonase (PON) activities were measured, and the MPO/PON ratio was then calculated. The lipid profiles and dysfunctional HDL levels in the healthy and patient groups were compared. Finally, the relationship between these parameters and the PRVEP-P100 wave latency was examined. Total cholesterol and low-density lipoprotein (LDL) levels were significantly higher in the patient group (P = .044; P = .038, respectively). There was no statistically significant difference in HDL levels between groups (P = .659). The distribution of MPO values was similar between groups (P = .452). PON values were significantly lower, whereas the MPO/PON ratios were significantly higher in the patient group than in the control group (P = .025; P = .028, respectively). A statistically significant positive correlation was found between the elevated MPO/PON ratio, representing dysfunctional HDL, and both the mean and maximum PRVEP-P100 wave latencies (P < .001, R = 0.690; P < .001, R = 0.815, respectively). A dysfunctional form of HDL may lead to poor deactivation of remyelination-limiting factors and may ultimately be associated with poor outcomes in optic neuritis.

Physical frailty is related to oxidative stress through thiol/disulfide homeostasis parameters.

AIM: To evaluate relationship between frailty and oxidative stress through thiol/disulfide homeostasis parameters [Native thiol (NT), total thiol (TT), and disulfide levels (D), disulfide-native thiol (D/NT), disulfide-total thiol (D/TT), native thiol-total thiol (NT/TT) ratios, and ischemia-modified albumin levels (IMA)]. MATERIALS AND METHODS: In total, 139 community-dwelling older adults were included. The frailty status, defined by the FRIED frailty index (FFI) and Clinical Frailty Scale (CFS), and comprehensive geriatric assessment results compared with thiol/disulfide homeostasis parameters and ischemia-modified albumin levels. RESULTS: NT and TT levels were significantly lower in the frail group (respectively; p = 0.014, p = 0.020). The FFI scores were correlated with the levels of NT, TT, D/NT, D/TT, and NT/TT (respectively; r = - 0.25, r = - 0.24, r = 0.17, r = 0.17, r = - 0.17). The significant correlation could not be retained with the CFS scores. In ROC analysis, the AUC for NT was calculated as 0.639 in diagnosing frailty according to the FFI (95% CI 0.542-0.737), AUC was 0.638 for TT (95% CI 0.540-0.735), and AUC was 0.610 for NT/TT (95% CI 0.511-0.780). The AUC was calculated as 0.610 for both D/NT and D/TT in diagnosing physical frailty (95% CI 0.511-0.708). CONCLUSION: Thiol/disulfide homeostasis parameters can be a potential biomarker in diagnosing physical frailty. However, further studies are needed for diagnosing frailty defined with cumulative deficit models.

Thiol-Disulphide Homeostasis, Ischemia-Modified Albumin, Trace Elements and Vitamins in Vitiligo Patients.

Background: Vitiligo, a multifactorial, depigmented skin disease, is characterised by selective loss of functional melanocytes leading to pigment reduction in the affected areas of the skin. Aim: We aimed to examine thiol-disulphide homeostasis, IMA, copper, zinc, selenium, vitamin A and vitamin C levels in vitiligo patients. Materials and Methods: The study included 83 vitiligo patients and 72 healthy controls. Copper, zinc, and selenium levels were measured by atomic absorption spectrophotometer; vitamin A and E levels were measured by high-performance liquid chromatography. Ischemia-modified albumin and native/total thiol levels were measured by colourimetric method. Results: Serum native and total thiol levels were significantly lower in vitiligo patients (P < 0.001, for all). Zn levels were significantly higher in vitiligo patients than in the control group (P = 0.004). There was no statistical difference in terms of Cu, Se, vitamin A and vitamin E levels. Conclusions: All thiol-disulphide homeostasis parameters (the most important antioxidant-oxidant system in circulation), trace elements, and vitamins together were evaluated in the present study in vitiligo patients. It can be concluded that vitiligo patients have increased oxidative stress status, and also the increase in the dissemination of the disease also increases the oxidative stress in the body.

A New Perspective for Potential Organ Damage Due to Iron-Mediated Oxidation in Thalassemia Major Patients.

BACKGROUND: The aim of this study is to develop new perspectives to prevent or reduce potential organ damage due to iron-mediated oxidation in thalassemia major patients. METHODS: Seventy patients were included in this study. Blood samples were taken from the patients before and after transfusion. Total thiol, native thiol, disulfide, disulfide/native thiol percentage ratio, ischemia modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS), and ferroxidase levels were determined. Additionally, undepleted thiol level (UTL) was determined as a new parameter associated with organ damage. RESULTS: After transfusion, the levels of native thiol, total thiol, disulfide, TAS, ferroxidase, and TOS were higher, while the IMA levels and disulfide/native thiol percent ratio were lower. Significant correlations were found between antioxidant and oxidant tests before and after transfusion. Additionally, a negative correlation was found between the TOS and UTL levels of the patients measured before the transfusion. CONCLUSION: In the present study, transfusion therapy increased both oxidation and the antioxidant levels. In addition, the term UTL has been introduced as a parameter that enables the determination of the oxidation level that may cause potential organ damage in transfusion-dependent thalassemia patients.

Evaluation of Oxidative Stress by Dynamic Thiol/Disulfide Homeostasis and Ischemia-Modified Albumin Levels in Children with ß-Thalassemia Major.

OBJECTIVE: ß-thalassemia major (ß-TM) is a hemoglobinopathy characterized by reduced or absent ß-globin production. A balance remains between the production of free radicals and suppression of increased levels of reactive oxygen species by the antioxidant system. This study aimed to examine thiol/disulfide homeostasis (TDH) and serum ischemia-modified albumin (IMA) levels to evaluate the oxidant/antioxidant balance in healthy children and persons with ß-TM receiving and not receiving chelation therapy. METHODS: This prospective study was carried out from January to June 2021 among 46 individuals with ß-TM and 35 healthy controls. A spectrophotometric method was used to analyze TDH and IMA concentrations. RESULTS: We found that, compared to controls, native thiol (NT) (P = .048) and total thiol (TT) (P = .027) values were lower in the patient group, whereas disulfide (P < .001), disulfide/native thiol (D/NT) (P = .004), disulfide/total thiol (D/TT) (P = .005), native thiol/total thiol (NT/TT) (P = .004) and IMA (P = .045) values were higher. NT and TT levels were significantly lower in the chelation- group compared to the chelation+ and control groups (P = .002, P = .001). D/NT, D/TT, and NT/TT levels were higher in the chelation+ group than the control group (P = .007), and IMA levels were significantly higher in the chelation+ and chelation- groups compared to the control group (P = .002). The receiver operating characteristic analysis demonstrated that IMA levels were significantly higher in the children with ß-TM not taking regular chelation therapy. CONCLUSION: Thiol/disulfide homeostasis was observed to be weakened in children with ß-TM in our study. Our findings show that when children with ß-TM do not receive regular chelation therapy, their oxidant imbalance worsens.

Evaluation of Oxidative Stress by Thiol/Disulphide Homeostasis in Patients with Mycosis Fungoides: A Prospective Double-Centre Study.

Background: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma with unknown etiopathogenesis. Oxidant and antioxidant balance is important for cell function and normal metabolism. An imbalance between pro-oxidants and antioxidants causes oxidative stress. A recent focus has been on thiol/disulphide homeostasis as a novel marker of oxidative stress. Aims and Objectives: This study aimed to evaluate the role of oxidative stress in MF by analysing thiol/disulphide homeostasis. Materials and Methods: A total of 103 patients (48 female, 55 male) and a control group of 120 healthy individuals (48 female, 72 male) from two tertiary care hospitals were included in our study. Serum native thiol, total thiol and disulphide levels were evaluated using novel method developed by Erel and Neeliolu. Results: Native thiol levels were 340.30 ± 87.44 in the patient group and 401.62 ± 69.45 in the control group. Total thiol value was 374.17 ± 87.78 in the patient group and 428.54 ± 70.05 in the control group. Native thiol and total thiol levels were significantly lower in the patient group compared to the control group (P < 0.001 and P < 0.001). The disulphide value was 16.93 ± 6.46 in the patient group and 13.46 ± 5.06 in the control group. Disulphide levels were found to be significantly higher in the patient group compared to the control group (P < 0.001). Conclusions: In our study, thiol/disulphide balance shifted towards disulphide which indicates the presence of oxidative stress especially in the early stage while 93.2% of our patients had early-stage MF. We think that this may have pathogenetic and prognostic significance.

Evaluation of thiol/disulfide hemostasis and serum Ischemia modified albumin as oxidative stress biomarkers in systemic lupus erythematosus patients: Relationship with major organ involvement and disease activity.

OBJECTIVES: We aimed to compare thiol/disulfide hemostasis and serum ischemia-modified albumin (IMA) levels, which are indicators of oxidative stress (OS), in patients with systemic lupus erythematosus (SLE), with the healthy control (HC) group and to evaluate the relationship of these parameters with disease activity and major organ involvement. MATERIAL-METHODS: Eighty-four SLE patients and 96 HCs were included in this study. The disease activity of SLE patients was calculated using The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Patients with SLEDAI-2K ≤ 5 were classified as low disease activity (LDA) and those with SLEDAI-2K > 6 as high disease activity (HDA). Thiol/disulfide hemostasis was evaluated using a new automated method and natural thiol (NT), total thiol (TT), disulfide (SS) levels, SS/NT, SS/TT, NT/TT ratios, and serum IMA levels were recorded. RESULTS: NT and TT levels were significantly lower (490.11 ± 123.61 vs 536.96 ± 86.05, p = 0.003) (532.56 ± 125.80 vs 565.72 ± 89.82, p = 0.046), SS level (21.22 ± 11.75 vs 13.37 ± 9.31, p < 0.001) was higher, and SS/TT (4.64 ± 2.93 vs 2.52 ± 1.82, p < 0.001) and SS/NT (4.12 ± 2.33 vs 2.35 ± 1.59, p < 0.001) ratios were significantly higher in SLE patients compared to HCs. IMA values were not different between the two groups (p = 0.920). NT (449.84 ± 136.98 vs 520.32 ± 104.11, p = 0.012) and TT levels (492.01 ± 138.45±562.97 ± 107.09, p = 0.013) were significantly lower and serum IMA levels (0.802 ± 0.089 vs 0.764 ± 0.040, p = 0.023) were significantly higher in SLE patients with HDA than in LDA patients. There was a weak negative correlation between NT (r = -0.284, p=0.009) (r = -0.291, p = 0.007) and TT levels (r = -0.281, p = 0.010) (r = -0.289, p = 0.008) and a weak positive correlation between IMA levels (r = 0.279, p = 0.011) (r = 0.263, p = 0.016) and SLEDAI-2K, and major organ involvement. CONCLUSION: It is thought that thiol/disulfide hemostasis and IMA levels may be used as ideal biomarkers of OS in SLE patients and may reflect the disease activity and major organ involvement.

Dynamic Thiol-Disulfide Homeostasis in Children With ß-Thalassemia Trait.

In children with ß-thalassemia (ß-thal) trait, tissue damage occurs with oxidative stress due to oxygen free radicals and reactive oxygen species (ROS) production. Dynamic thiol-disulfide homeostasis (DTDH) is one of the most important indicators showing the pro-oxidant/antioxidant status in the body. In this study, we aimed to examine the status of DTDH by measuring native thiol, disulfide, and total thiol levels in children with ß-thal trait. The study included 40 children with ß-thal trait and 30 healthy controls (matched by age and gender). The DTDH parameters were measured by an automated method and results were compared between the groups. The levels of native thiol, total thiol, and disulfide in children with ß-thal trait group were statistically significantly higher than the control group (p < 0.001). There was no significant difference in disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol levels between the groups. In addition, there was no correlation between hemoglobin (Hb) and serum ferritin levels with the markers of DTDH in children with ß-thal trait. In our study, a significant increase was found in native thiol, total thiol, and disulfide levels in response to oxidative stress in children with ß-thal trait compared to the healthy control group. Disulfide levels of the children with ß-thal trait were higher than the control group, showing oxidative stress is high in ß-thal trait. Accordingly, it increases the native thiol and total thiol capacity as compensation.

Comparison of three different HbA1c measurement methods - the Atellica®CH930, Capillary 3 Tera, and BioRad Variant Turbo II.

AIM: HbA1c measurement is very useful for the follow-up and detection of glycemic disorder, since it is easier and faster test and is independent of the patient's fasting status. In this study, we aimed to perform the comparative evaluation of 3 different methods for HbA1c measurement including capillary electrophoresis, immunoturbidimetric assay and high-performance liquid chromatography-HPLC. MATERIALS AND METHODS: This study comprised 134 leftover whole blood samples obtained from the subjects submitted for routine HbA1c testing. All blood samples were collected in EDTA-containing vacutainer tubes. The HbA1c levels were measured simultaneously using three different methods. Bias estimation, method agreement and concordance between the pairwise methods comparisons were evaluated by Bland-Altman plot and Passing-Bablok regression test. RESULTS: HbA1c levels ranged from 3.8% to 13.4% and measured by three different methods to make the comparison. The median values of samples based on immunoturbidimetric method (6.05%, IQR = 1.80) were higher than capillary electrophoresis method (5.90%, IQR = 1.80) and HPLC (5.85%, IQR = 1.80) method. The study group was classified into three subgroups based on the HbA1c levels measured with the HPLC method: Group 1 (n = 57) was composed of subjects with HbA1c levels less than 5.7%, Group 2 (n = 35) had HbA1c levels between 5.7% and 6.4%, Group 3 (n = 42) had HbA1c levels equal and more than 6.5%. CONCLUSION: To our knowledge, there is no study evaluating the HbA1c measurement on the Atellica® CH 930 Analyzer. We compared the Atellica®CH930 Analyzer with both HPLC and capillary electrophoresis. The Atellica®CH930 Analyzer showed acceptable performance and a strong correlation with both mentioned methods.

Serum IL-17 levels in patients with rosacea.

BACKGROUND: Rosacea is a chronic inflammatory skin disease characterized with increased serum and tissue inflammatory mediators. IL-17 is a well-known inflammatory mediator that plays important roles in pathogenesis of inflammatory skin diseases. Previous studies reported that Th17 pathway is activated in rosacea and IL-17, one of Th17 signature cytokines, is elevated in tissue samples of rosacea patients. OBJECTIVES: The aim of this study was to investigate serum IL-17 levels in rosacea patients and to study its relationship with disease characteristics. METHODS: Sixty patients diagnosed with rosacea and 60 healthy controls were included in the study. Serum IL-17 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean serum IL-17 level was 8.03 pg/mL (SD = 1.47) in rosacea patients and 7.37 pg/mL (Sd = 1.19) in controls. Serum IL-17 levels were significantly higher in rosacea (p = 0.002). Serum IL-17 levels were similar among patients with erythematotelangiectatic (ET) and papulopustular (PP) rosacea (8.02 vs 8.06, p = 0.83). Serum IL-17 levels did not correlate with rosacea severity (p = 0.59, r = 0.07 in ET rosacea; p = 0.88, r = 0.02 in PP rosacea), age of onset (p = 0.58, r = -0.07), and disease duration (p = 0.37, r = -0.11). Primary features and global assessments did not correlate with serum IL-17 levels (all p > 0.05). Among secondary features, edema showed a significant negative correlation with serum IL-17 concentrations (p = 0.037, r = -0.26). CONCLUSIONS: Our study showed increased serum IL-17 levels in rosacea patients and a significant correlation between IL-17 concentrations and secondary features of the disease suggesting IL-17 may contribute to pathogenesis of rosacea and may be a new target for rosacea treatment.

Investigation of plasma thiol/disulfide balance in male patients with androgenetic alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is the most common cause of hair loss in men. In addition to genetic and hormonal factors, oxidative stress (OS) is suggested as a factor in the etiology. AIM: In this study, we aimed to investigate the presence of OS due to thiol disulfide balance deterioration in male patients with AGA. MATERIALS AND METHODS: A total of 45 male AGA patients and 42 healthy male controls were included in the study. Native thiol, disulfide, and total thiol levels were assessed through automated spectrophotometry. The relationship between total protein, albumin, native thiol, disulfide, and total thiol levels in addition to demographic and clinical characteristics of the patients were examined. RESULTS: The mean age of the patients was 32.6 ± 10 years, and the median AGA duration in the patients was 3 years. There was no statistically significant difference in terms of native thiol, disulfide, total thiol levels, disulfide/total thiol, disulfide/native thiol, and native thiol/total thiol ratios between AGA patients and controls. Native thiol and total thiol levels negatively correlated with age and AGA duration, while disulfide levels only correlated with age.Albumin and native thiol levels were significantly lower in patients with low vitamin D levels (p = 0.040 and p = 0.021, respectively); however, total thiol and native thiol/total thiol ratio values were significantly higher. CONCLUSION: According to this study, thiol disulfide homeostasis is in balance in male patients with AGA. In patients with emotional stress and vitamin D deficiency, the balance appears to be shifted in favor of oxidative stress.

Can Serum Endocan Levels be Used as an Early Prognostic Marker for Endothelial Dysfunction in COVID-19?

In this study, we aimed to investigate whether degree of pneumonia and COVID-19 prognosis are associated with serum endocan levels at the early stage, when vascular damage has started. Patients between the ages of 18-85 years who were hospitalized and followed up with a diagnosis of COVID-19 were included in the study. A total of 80 patients were divided into 2 groups as mild/moderate pneumonia and severe pneumonia. Serum endocan levels were measured on the 8th day from the onset of symptoms in all patients. Of the 80 patients included in the study, 56.3% were female and 43.8% were male. There was no significant relationship between serum endocan levels and degree of pneumonia (P = .220) and prognosis of the disease (P = .761). The correlation analysis indicated a weak positive correlation between serum endocan levels and lactate level in venous blood gas (r = .270; P = .037). During the 28-day follow-up, the mortality rate was 3.75%. It was determined that the serum endocan levels was not associated with the degree of pneumonia and was not an early prognostic marker for COVID-19.

Clinicoradiological evaluation of oxidative stress activity in acute cerebral infarction in the first 24 h and the qualitative importance of dysfunctional HDL in stroke.

BACKGROUND: Acute cerebral infarction (ACI) occurs as a result of instant disruption of vascular flow that causes disbalance between oxidative/antioxidative activity. We examined the relationship of serum neuro-oxidative stress parameters with stroke severity and infarct volume in ACI and emphasized the qualitative importance of high-density lipoprotein (HDL) on its relationship with myeloperoxidase (MPO) and paraoxonase-1 (PON1) in the acute period of stroke. METHODS: One hundred ACI patients applied within the first 24 h and 50 healthy volunteers were included. The patient group was evaluated with demographic data (including arrival serum biochemical assessment), clinical disability scores, infarct volume, serum oxidative/antioxidative parameters (lipid hydroperoxide (LOOH), MPO, PON1, MPO/PON ratio). The relevant serum parameters were compared with the control group. Dysfunctional HDL measurement was based on detecting dysfunctionality as a result of a high positive correlation between the dysfunctional feature of HDL and the MPO/PON ratio. The correlation of serum parameters, clinical disability score, and infarct volume were evaluated, and independent analyses of variability with comorbidities were performed. RESULTS: A negative correlation between PON1 and arrival NIH score/scale (NIHSS), LOOH and discharge modified rankin scale (mRS), triglyceride level, and infarct volume; a positive correlation between MPO\PON ratio and infarct volume was determined. Logistic regression analyses showed that hypertension, diabetes, and high HbA1C may be predictors of stroke severity, and diabetes mellitus, high HbA1C, infarct volume, and high NIHSS score may be predictors of early disability (p < 0.005). The ROC curve analysis revealed that determining the cut-off value for LOOH is of importance in determining early disability scores (7.2 and 6.2, respectively). DISCUSSION: The balance between oxidative and antioxidative stress parameters and their quantitative/qualitative changes is of importance, especially in the acute period of ACI. Dysfunctional HDL's evolution and its relationship with other oxidants are significant not only in the cardiovascular aspect but also in the clinicoradiological aspect.

The response of total testing process in clinical laboratory medicine to COVID-19pandemic.

INTRODUCTION: Following a pandemic, laboratory medicine is vulnerable to laboratory errors due to the stressful and high workloads. We aimed to examine how laboratory errors may arise from factors, e.g., flexible working order, staff displacement, changes in the number of tests, and samples will reflect on the total test process (TTP) during the pandemic period. MATERIALS AND METHODS: In 12 months, 6 months before and during the pandemic, laboratory errors were assessed via quality indicators (QIs) related to TTP phases. QIs were grouped as pre-, intra- and postanalytical. The results of QIs were expressed in defect percentages and sigma, evaluated with 3 levels of performance quality: 25th, 50th and 75th percentile values. RESULTS: When the pre- and during pandemic periods were compared, the sigma value of the samples not received was significantly lower in pre-pandemic group than during pandemic group (4.7σ vs. 5.4σ, P = 0.003). The sigma values of samples transported inappropriately and haemolysed samples were significantly higher in pre-pandemic period than during pandemic (5.0σ vs. 4.9σ, 4.3σ vs. 4.1σ; P = 0.046 and P = 0.044, respectively). Sigma value of tests with inappropriate IQC performances was lower during pandemic compared to the pre-pandemic period (3.3σ vs. 3.2σ, P = 0.081). Sigma value of the reports delivered outside the specified time was higher during pandemic than pre-pandemic period (3.0σ vs. 3.1σ, P = 0.030). CONCLUSION: In all TTP phases, some quality indicators improved while others regressed during the pandemic period. It was observed that preanalytical phase was affected more by the pandemic.

A sensitive indicator for the severity of COVID-19: thiol

Background/aim: Thiol status is a good reflector of the cellular redox and have vital roles in various cellular signaling pathways. The purpose of the study was to investigate thiol status in patients with SARS-CoV-2 infection. Materials and methods: A total of 587 subjects (517 patients/70 healthy controls) were enrolled in the study.The patients were categorized into the groups regarding to the severity of disease (mild, moderate, severe, and critical).Thiol status of all groups were compared. Results: The patients had significantly diminished thiol levels compared to controls. Thiol levels were gradually decreased as the severity of the disease increased. Logistic regression analyses identified that thiol concentrations were an independent risk factor for the disease severity in each phase (mild group OR 0.975, 95%CI 0.965-0.986; moderate group, OR 0.964, 95%CI 0.953-0.976; severe group OR 0.953, 95%CI 0.941-0.965; critical group OR 0.947, 95%CI 0.935-0.960).Thiol test exhibited the largest area under the curve at 0.949, with the highest sensitivity (98.6%) and specificity (80.4%). Conclusions: Depleted thiol status was observed in SARS-CoV-2 infection. Decline of the thiol levels by degrees while the severity of infection increased was closely related to the progression of the disease. This outcome highlights that thiols could be an impressible biomarker for predicting of the severity of COVID-19.

Electrolyte, Nitric Oxide and Oxidative Stress Levels of Aqueous Humor in Patients with Retinal Detachment and Silicone Oil Tamponade.

Purpose: To enlighten the pathogenesis of silicone oil (SiO)-related complications via measuring aqueous humor levels of electrolytes, nitric oxide (NO), and oxidative stress in SiO, retinal detachment (RD), and control groups. Materials and Methods: In this prospective study, 56 patients were grouped as SiO (n = 29), RD (n = 12), and control (n = 15). The results of pre- and post-operative ophthalmological examinations, aqueous humor electrolyte and NO levels, total antioxidant and oxidant status (TAS, TOS) and oxidative stress index (OSI) were analyzed. Results: SiO group had a higher mean Na+ level compared to controls (144.77 ± 11.48 vs 137.56 ± 6.57 mmol/kg, p = .02). Also, the mean Na+ and Cl- levels of RD group were higher than controls (149.04 ± 12.05 vs. 137.56 ± 6.57 mmol/kg, p = .02, 115.2 ± 7.79 vs 106.23 ± 8.99 mmol/kg, p = .031 for Na+ and Cl-, respectively). The mean NO level of RD group was higher than that of SiO group (51.07 ± 19.56 vs. 34.07 ± 13.84 µM, p = .009). The mean TAS and TOS were lower in SiO group compared to controls (1.92 ± 0.64 vs. 2.49 ± 0.56 µmolTroloxEqv./L, p = .021, 34.98 ± 26.55 vs. 61.46 ± 22.69 µmolH2O2Eqv./L, p = .004 for TAS and TOS, respectively). Intraocular retention time of SiO demonstrated positive correlation with post-operative visual acuity (logMAR) and negative correlation with TOS. Conclusions: Elevated aqueous humor Na+ and Cl- in RD patients might reflect abolished function of ion channels on detached retina. Increased Na+ and lack of NO response to elevated intraocular pressure in SiO-filled eyes might contribute to secondary cataract and glaucoma formation. SiO is associated with low levels of oxidative stress in aqueous humor; however, increased intraocular retention time of SiO is related to a poor visual outcome.

PPP2R3C gene variants cause syndromic 46,XY gonadal dysgenesis and impaired spermatogenesis in humans.

Context Most of the knowledge on the factors involved in human sexual development stems from studies of rare cases with disorders of sex development. Here, we have described a novel 46, XY complete gonadal dysgenesis syndrome caused by homozygous variants in PPP2R3C gene. This gene encodes B″gamma regulatory subunit of the protein phosphatase 2A (PP2A), which is a serine/threonine phosphatase involved in the phospho-regulation processes of most mammalian cell types. PPP2R3C gene is most abundantly expressed in testis in humans, while its function was hitherto unknown. Patients and methods Four girls from four unrelated families with 46, XY complete gonadal dysgenesis were studied using exome or Sanger sequencing of PPP2R3C gene. In total, four patients and their heterozygous parents were investigated for clinical, laboratory, immunohistochemical and molecular characteristics. Results We have identified three different homozygous PPP2R3C variants, c.308T>C (p.L103P), c.578T>C (p.L193S) and c.1049T>C (p.F350S), in four girls with 46, XY complete gonadal dysgenesis. Patients also manifested a unique syndrome of extragonadal anomalies, including typical facial gestalt, low birth weight, myopathy, rod and cone dystrophy, anal atresia, omphalocele, sensorineural hearing loss, dry and scaly skin, skeletal abnormalities, renal agenesis and neuromotor delay. We have shown a decreased SOX9-Phospho protein expression in the dysgenetic gonads of the patients with homozygous PPP2R3C variants suggesting impaired SOX9 signaling in the pathogenesis of gonadal dysgenesis. Heterozygous males presented with abnormal sperm morphology and impaired fertility. Conclusion Our findings suggest that PPP2R3C protein is involved in the ontogeny of multiple organs, especially critical for testis development and spermatogenesis. PPPR3C provides insight into pathophysiology, as well as emerging as a potential therapeutic target for male infertility.

Minimally invasive thyroid anaplastic carcinoma with long survival.

Anaplastic thyroid carcinoma is a highly lethal malignancy. Previously, only five cases of a noninvasive form of anaplastic thyroid carcinoma with excellent prognosis were reported. We report a case of a 68-year-old man who presented with a 3.8 cm thyroid nodule diagnosed by fine needle aspiration biopsy as poorly differentiated spindled and epithelial malignant cells. Lobectomy and isthmusectomy were performed, and the final diagnosis was microinvasive anaplastic thyroid carcinoma arising in a poorly differentiated carcinoma. The patient remains disease-free after six years, even after hemithyroidectomy and radiation treatment. Noninvasive/microinvasive anaplastic thyroid carcinoma appears to be a different disease entity from classical anaplastic thyroid carcinoma, with favorable prognosis and long disease-free survival.