Explainable artificial intelligence for LDL cholesterol prediction and classification.

INTRODUCTION: Monitoring LDL-C levels is essential in clinical practice because there is a direct relation between low-density lipoprotein cholesterol (LDL-C) levels and atherosclerotic heart disease risk. Therefore, measurement or estimate of LDL-C is critical. The present study aims to evaluate Artificial Intelligence (AI) and Explainable AI (XAI) methodologies in predicting LDL-C levels while emphasizing the interpretability of these predictions. MATERIALS AND METHODS: We retrospectively reviewed data from the Laboratory Information System (LIS) of Ankara Etlik City Hospital (AECH). We included 60.217 patients with standard lipid profiles (total cholesterol [TC], high-density lipoprotein cholesterol, and triglycerides) paired with same-day direct LDL-C results. AI methodologies, such as Gradient Boosting (GB), Random Forests (RF), Support Vector Machines (SVM), and Decision Trees (DT), were used to predict LDL-C and compared directly measured and calculated LDL-C with formulas. XAI techniques such as Shapley additive annotation (SHAP) and locally interpretable model-agnostic explanation (LIME) were used to interpret AI models and improve their explainability. RESULTS: Predicted LDL-C values using AI, especially RF or GB, showed a stronger correlation with direct measurement LDL-C values than calculated LDL-C values with formulas. TC was shown to be the most influential factor in LDL-C prediction using SHAP and LIME. The agreement between the treatment groups based on NCEP ATPIII guidelines according to measured LDL-C and the LDL-C groups obtained with AI was higher than that obtained with formulas. CONCLUSIONS: It can be concluded that AI is not only a reliable method but also an explainable method for LDL-C estimation and classification.

Concordance and generalization of an AI algorithm with real-world clinical data in the pre-omicron and omicron era.

All viruses, including SARS-CoV-2, the virus responsible for COVID-19, continue to evolve, which can lead to new variants. The objective of this study is to assess the agreement between real-world clinical data and an algorithm that utilizes laboratory markers and age to predict the progression of disease severity in COVID-19 patients during the pre-Omicron and Omicron variant periods. The study evaluated the performance of a deep learning (DL) algorithm in predicting disease severity scores for COVID-19 patients using data from the USA, Spain, and Turkey (Ankara City Hospital (ACH) data set). The algorithm was developed and validated using pre-Omicron era data and was tested on both pre-Omicron and Omicron-era data. The predictions were compared to the actual clinical outcomes using a multidisciplinary approach. The concordance index values for all datasets ranged from 0.71 to 0.81. In the ACH cohort, a negative predictive value (NPV) of 0.78 or higher was observed for severe patients in both the pre-Omicron and Omicron eras, which is consistent with the algorithm's performance in the development cohort.

Comparison of the Two Coagulation Techniques: Thrombolyzer XRM and Diagon Coag XL.

BACKGROUND: The aim of this study was to evaluate the performance characteristics of the Thrombolyzer XRM against the Diagon Coag XL during the exchange of the coagulation analyzer. METHODS: The Partial Thromboplastin Time (PTT) and prothrombin time (PT) measurements were performed by using the Thrombolyzer XRM and Diagon CoagXL analyzers. The precision, accuracy, method comparison, and reference range verification studies were performed on the Thrombolyzer XRM based on Clinical Laboratory Standards Institute guidelines. RESULTS: The precision study was performed with normal and pathologic controls for the PT and PTT tests, all co-efficients of variation (%) were found ≤ 2.5%. In the accuracy study, both analyzers displayed less than 6.3% and 10.8% bias for PT and PTT tests, respectively. The method comparison study demonstrated good agreement for the Bland-Altman plots for PTT and PT with a bias of -2.0 and -3.3 between each analyzer, respectively. The Passing and Bablok analysis showed no significant differences for PTT and PT between each analyzer (p = 0.65 and p = 0.33, respectively). However, there was a proportional bias for PT with a slope of 1.40 (95% CI 1.2 - 1.8). The manufacturer ranges were acceptable as a result of the reference range verification study. CONCLUSIONS: The routine coagulation analysis can be performed on the Thrombolyzer XRM with satisfactory precision and the obtained minor differences can be eliminated in future standardization studies.

Lipemia impact on HBA1C measurements in patients with and without hemoglobin variant: a rational laboratory use evaluation.

This study aims to compare the HbA1c test results obtained by widely used methods using samples with various lipemia levels and Hb variants, and to determine whether it is possible to correct the lipemia effect in the identical samples. Out of the laboratory information system (LIS), 48 patients with various HbA1c results were identified including patients with and without Hb variants. After the baseline measurements, all samples were spiked with intralipid solution and treated by a subsequent 0.9% saline replacement procedure. HbA1c values were measured four times sequentially with enzymatic and capillary electrophoresis (CE) methods for each sample, and the measurements were categorized as follows: Baseline; Spiked, 5g/L; Spiked, 20g/L; Post-saline replacement. Sequential HbA1c measurements using the CE method did not show a significant difference, but samples containing 20 g/L triglycerides and samples treated with 0.9% saline replacement showed a significant difference when compared to baseline measurements in both patients with and without Hb variants using the enzymatic method (p < 0.001). The correlation between the two methods was strong at baseline measurements (r = 0.977), declined with lipemia (r = 0.968 and r = 0.737 for 5 g/L and 20 g/L triglycerides, respectively), and then increased with 0.9% saline replacement (r = 0.962) in patients without Hb variants. This study revealed that the enzymatic method, but not CE was susceptible to lipemia interference both in patients with and without Hb variants. Lipemia interference could be partially eliminated with 0.9% saline replacement, but enzymatic measurements were still somewhat affected.

The effect of acid use as a preservative on the results of biochemical tests measured in 24-h urine.

Twenty-four-hour urine measurements play a crucial role in the diagnosis, follow-up and treatment of various diseases. There are different approaches to the collection of urine in patients who need to collect multiple urine samples at a time, especially in hospitals with heavy workloads. In this study, we compared the sodium, potassium, chloride, amylase, calcium, creatinine, phosphorus, microalbumin, protein, magnesium, urea, uric acid, adrenaline, noradrenaline, dopamine, metanephrine, normetanephrine, vanillylmandelic acid, 5-hydroxyindoleacetic acid and homovanillic acid results of 24-h urine samples analyzed immediately without acid addition, which we accepted as the reference and baseline measurement, with the results of the samples analyzed after waiting for 24 h without acid addition, analyzed immediately with acid addition and analyzed after waiting for 24 h with acid addition. Chloride, microalbumin, amylase and protein tests, which are recommended to be measured in the sample without preservatives, are affected by acid addition. Adrenaline, noradrenaline and dopamine, which are the tests recommended to be measured in acid-added urine are degraded in the samples without acid, and the levels of metanephrine and normetanephrine were not significantly degraded in the absence of preservatives.

COVID-19 patients with altered steroid hormone levels are more likely to have higher disease severity.

PURPOSE: This study aims to evaluate the correlations between the severity of the disease and serum steroid levels by analyzing the serum steroid levels in COVID-19 patients with different levels of disease progression and the control group. METHODS: Morning serum Aldosterone, 11-deoxycortisol, Androstenedione, 17-hydroxyprogesterone, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA), Corticosterone, Dehydroepiandrosterone sulfate (DHEAS), Estrone, Estradiol, Progesterone, 11-deoxycorticosterone, Cortisol, Corticosterone, Androsterone, Pregnenolone, 17-hydroxypregnenolone and 21-deoxycortisol levels were measured in 153 consecutive patients were grouped as mild, moderate, and severe based on the WHO COVID-19 disease severity classification and the control group. Steroid hormone levels were analyzed at once with a liquid chromatography-tandem mass spectrometric method (LC-MS/MS). RESULTS: In our study, nearly all steroids were statistically significantly higher in the patients' group than in the control group (p < 0.001). Also, DHEA was an independent indicator of the disease severity with COVID-19 CONCLUSIONS: Our study reveals that the alteration in steroid hormone levels was correlated with disease severity. Also, steroid hormone levels should be followed up during COVID-19 disease management.

Assessment of Galectin-1, Galectin-3, and Prostaglandin E2 Levels in Patients with COVID-19.

It is important to determine the inflammatory biomarkers in the severity of coronavirus disease 2019 (COVID-19) with the emergence of the pandemic. Galectins and prostaglandins play important roles in the regulation of immune and inflammatory responses. Therefore, this study aimed to investigate Galectin-1 (Gal-1), Galectin-3 (Gal-3), and prostaglandin E2 (PGE2) levels in patients with COVID-19. Serum concentrations of Gal-1, Gal-3, and PGE2 were measured using enzyme-linked immunosorbent assay on 84 patients with COVID-19 (severe = 29 and nonsevere = 55) and 56 healthy controls. In this study, increased levels of Gal-1 (median, 9.86, 6.35, and 3.67 ng/mL), Gal-3 (median, 415.31, 326.33, and 243.13 pg/mL), and PGE2 (median, 193.17, 192.58, and 124.62 pg/mL) levels were found in patients with COVID-19 than in healthy controls (P < 0.001 for all). In the severe disease group, Gal-3 levels were higher, while no differences were noted in Gal-1 and PGE2 levels (P = 0.011, P = 0.263, and P = 0.921, respectively). Serum levels of Gal-1 were positively correlated with those of Gal-3 (P = 0.871 and P < 0.001). Gal-3, C-reactive protein, lymphocyte count, and age were found as independent predictors of disease severity (P = 0.002, P = 0.001, P = 0.007, and P = 0.003, respectively). With the emergence of effective drug needs in the COVID-19 pandemic, differentiation of severe disease is important. Therefore, Gal-3 could be a potential prognostic biomarker of COVID-19.

Evaluation of the diagnostic performance of an oral fluid screening test device for substance abuse at traffic controls.

INTRODUCTION: The aim of this study was to evaluate the analytical performance of the Kite Biotechnology Oral fluid (OF) screening test device, which is used for roadside screening of cannabis, opiates, amphetamines, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), cocaine and benzodiazepines by comparing samples with matched plasma samples, analysed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for confirmation. METHODS: OF and plasma samples were obtained simultaneously from a total of 100 subjects. OF samples were analysed by OF screening test based on immunochromatography. The OF screening test cut-off values were 50 ng/mL for amphetamines (d-amphetamine) and methamphetamine/MDMA (d-methamphetamine), 30 ng/mL for cocaine (benzoylecgonine), 40 ng/mL for opiates (morphine), 20 ng/mL for benzodiazepines (nordazepam), and 25 ng/mL for cannabis (Δ9-tetrahydrocannabinol). LC-MS/MS method validation was performed according to the CLSI C62-A recommendations with the following parameters: matrix effect, lower limit of quantification (LLOQ), linearity, intra-day and inter-day precision and accuracy. RESULTS: The overall specificity, accuracy and negative predictive values (NPV) were acceptable and met the DRUID standard of >80%. The OF screening test device showed good sensitivity for cocaine, amphetamines and opiates, whereas it indicated poor sensitivity for methamphetamine/MDMA (66.7%) and failed to detect cannabis and benzodiazepines. CONCLUSION: The present study is the first report to evaluate the Kite Biotechnology OF screening test device. The diagnostic performance of the OF screening test device was acceptable for opiates, cocaine and amphetamines, but it was insufficient for methamphetamine/MDMA, benzodiazepines and cannabis because of sensitivity issues.

Effects of Bone Marrow and Adipose-Derived Mesenchymal Stem Cells on microRNA Expressions in Acute Alkaline Corneal Burn.

Purpose: The aim of this study was to investigate the microRNA (miRNA) expressions of the corneal tissue after an alkaline burn and to compare the efficiency of adipose- and bone marrow-derived mesenchymal stem cells (MSCs) on expressions. Methods: Thirty-two rats were divided into 4 groups. No intervention was made in the control group. A chemical burn was created by applying 4 µL NaOH soaked in 6 mm filter paper to the right eye of each animal in the other groups. Whereas only subconjunctival 0.1 mL phosphate-buffered saline (PBS) was injected to in the group 1, 2 × 106 adipose- or bone marrow-derived MSC in 0.1 mL PBS was injected subconjunctivally to the animals in the remaining groups (groups 2 and 3, respectively). Tissue samples were collected for miRNA analysis on the third day after the burn. Results: When group 1 was compared with the control group, the expression of 3 of 93 miRNAs increased significantly, whereas the expression of 50 miRNAs decreased significantly. Significant changes in miRNA expressions were observed when group 1 was compared with groups 2 and 3. Although a significant change was observed in the expression of 6 miRNAs in the adipose-derived MSC group, it was found that the expression of 65 miRNAs significantly changed in the bone marrow-derived MSC group. Conclusion: This study shows that there are significant changes in some miRNA expressions after corneal alkaline burn and these changes can be reversed with the subconjunctival injection of MSCs.

Lymphocyte Subset Alteration and Monocyte CD4 Expression Reduction in Patients with Severe COVID-19.

The spectrum of coronavirus disease 2019 (COVID-19) severity, related to cellular immune functions, has not been fully clarified yet. Therefore, this study aimed to investigate the alteration of peripheral blood cells in patients with COVID-19. The flow cytometric characterization of immune cell subset was performed on 69 COVID-19 patients and 21 healthy controls. These data were evaluated based on the disease severity. A total of 69 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were classified as asymptomatic infection (n = 14), nonsevere (n = 39), and severe (n = 16) groups. Decreased lymphocytes and increased CD14 + 4- monocytes are found in patients with severe COVID-19. Decreased CD4 expression level was observed in the monocytes of patients with severe COVID-19. The total lymphocytes, B and T lymphocytes, CD4+ cells and CD8+ cells, and natural killer (NK) and natural killer T (NKT) cells were found to be decreased in patients with severe COVID-19. The CD4+/CD8+ ratio was not significantly different between patients with COVID-19 and healthy controls. The percentage of activated T cells (CD3+HLA-DR+) and B cells (CD19+CD38+) was lower in patients with severe COVID-19. Age and CD4- monocytes were independent predictors of disease severity. The SARS-CoV-2 infection may affect lymphocyte subsets, resulting in decreased T and B cells, monocytes, and NK and NKT cells. Decreased CD4 expression level by monocytes was significantly correlated with disease severity. Further studies on the host immune response to SARS-CoV-2 infection are necessary to predict the disease severity and protect against the virus.

Evaluation of Anti-Inflammatory and Antiapoptotic Effects of Bone Marrow and Adipose-Derived Mesenchymal Stem Cells in Acute Alkaline Corneal Burn.

Purpose: The aim of the present study is to comparatively evaluate the anti-inflammatory and antiapoptotic effects of bone marrow and adipose-derived mesenchymal stem cells (MSCs) applied subconjunctivally after alkaline corneal burn. Methods: Thirty-two rats were divided into 4 groups and included in the study (n = 8). While no intervention was made in the control group, a chemical burn was created by applying 4 µL of NaOH soaked in 6 mm filter paper to the right eye of each subject in the other groups under general anesthesia. While only subconjunctival 0.1 mL phosphate-buffered saline (PBS) was injected to in the group 1, 2 × 106 adipose or bone marrow-derived MSC in 0.1 mL PBS was applied subconjunctivally to the subjects in the remaining groups (Group 2 and 3, respectively). Tissue samples were collected for histological analysis on the third day after the burn. Tissue samples were evaluated light microscopically and immunohistochemically stained for interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), caspase-3 (Cas-3), and CD68. Results: The IL-1ß and TNF-α staining scores and the number of CD68- and Cas-3-positive stained cells were significantly lower in the groups given bone marrow and adipose-derived MSC compared to the alkaline burn group (P < 0.0001, for all parameters). Epithelial IL-1ß and TNF-α staining scores were significantly lower in the bone marrow-derived MSC group compared to the adipose-derived MSC group (P < 0.0001, for all parameters). Conclusions: The presented study shows that both bone-marrow and adipose-derived MSCs support wound healing in the corneal tissue and strongly suppress the inflammation occured in the tissue.

Clinical and laboratory features of COVID-19: Predictors of severe prognosis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged first in December 2019 in Wuhan, China and quickly spread throughout the world. Clinical and laboratory data are of importance to increase the success in the management of COVID-19 patients. METHODS: Data were obtained retrospectively from medical records of 191 hospitalized patients diagnosed with COVID-19 from a tertiary single-center hospital between March and April 2020. Prognostic effects of variables on admission among patients who received intensive care unit (ICU) support and those who didn't require ICU care were compared. RESULTS: Patients required ICU care (n = 46) were older (median, 71 vs. 43 years), with more underlying comorbidities (76.1% vs. 33.1%). ICU patients had lower lymphocytes, percentage of large unstained cell (%LUC), hemoglobin, total protein, and albumin, but higher leucocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocytes ratio (PLR), urea, creatinine, aspartate amino transferase (AST), lactate dehydrogenase (LDH), and D-dimer when compared with non-critically ill patients (p < 0.001). A logistic regression model was created to include ferritin, %LUC, NLR, and D-dimer. %LUC decrease and D-dimer increase had the highest odds ratios (0.093 vs 5.597, respectively) to predict severe prognosis. D-dimer, CRP, and NLR had the highest AUC in the ROC analysis (0.896, 0.874, 0.861, respectively). CONCLUSIONS: The comprehensive analysis of clinical and admission laboratory parameters to identify patients with severe prognosis is important not only for the follow-up of the patients but also to identify the pathophysiology of the disease. %LUC decrease and D-dimer, NLR, and CRP increases seem to be the most powerful laboratory predictors of severe prognosis.

Effects of 1,25-Dihydroxy vitamin D3 on TNF-α induced inflammation in human chondrocytes and SW1353 cells: a possible role for toll-like receptors.

The purpose of this study is to evaluate anti-inflammatory and chondro-protective effects of 1,25(OH)2D3 in human chondrocytes and SW1353 cells via investigating expressions of MMPs, TIMPs, VDR, and intracellular signalling pathway mediators such as TLR-2 and -4. The HC and SW1353 cells were treated with 1,25(OH)2D3 at 10, 100, and 1000 nM concentrations in the absence/presence of TNF-α (20 ng/mL) for 48 h. The mRNA expressions of MMP-1, -2, -3, -9, and -13, TIMP-1 and -2, VDR, TLR-2 and -4 in HC and SW1353 cells were detected by qPCR after treatments. The cytotoxicity and cell proliferation analyses were assessed by LDH and WST-1 assay, respectively. Protein levels of MMPs, TIMPs, and VDR were analysed by immunocytochemistry and ELISA methods. TNF-α markedly increased cytotoxicity for 24, 48, 72 h (p < 0.05) and vitamin D treatment was shown to diminish the cytotoxic effect of TNF-α. Cell proliferations increased by Vitamin D in a dose-dependent manner. mRNA expressions of MMP-1, -2, -3, -9, and -13, TLR-2 and -4 genes decreased with 1,25(OH)2D3 treatment (p < 0.05). VDR, TIMP-1 and -2 levels elevated after TNF-α exposure compared with the control group in HC cells (p < 0.05). Protein expression levels were determined using Western blotting, ELISA and immunocytochemistry. 1,25(OH)2D3 via binding to VDR, reversed the effects of TNF-α by inhibiting TLR-2 and 4. Decreased levels of VDR, TIMP-1 and -2 after TNF-α treatment were elevated by 1,25(OH)2D3 proportional with increasing 1,25(OH)2D3 doses. 1,25(OH)2D3 and TNF-α co-treatment decreased MMP-1, -2, -3, -9, and -13 levels were after TNF-α exposure.

Predictors of Language Dominance: An Integrated Analysis of First Language Attrition and Second Language Acquisition in Late Bilinguals.

Late bilinguals who spend (part of) their adult lives in an environment where a language other than the one they learned in childhood is spoken typically experience a range of language development phenomena. Most obviously, they will acquire some level of receptive and/or productive knowledge of the new, or second, language (L2). How basic or advanced that level will be is determined by a range of environmental, experiential, attitudinal and individual factors. Secondly, they will most likely find the knowledge of their native language (L1) beginning to diverge from that of monolingual speakers in their country of origin, a process known as language attrition. In the course of this developmental process, some L2 skills may eventually match or even overtake the corresponding skill in the L1. This shift in the balance between L1 and L2 is the focus of investigations of language dominance. The present study explores language dominance in four migrant populations (Germans in the Netherlands and Canada, Turks and Moroccans in the Netherlands). Investigating both the development of formal/controlled skills and more automatic aspects of lexical access and fluency, we aim to attain an understanding of how extralinguistic factors contribute to the development of both languages. We argue that an integrated perspective can contribute more profound insights into the predictors of this complex process of bilingual development. In particular, our findings show that statistical models based on linear relationships fall short of capturing the full picture. We propose an alternative method of analysing data, namely discriminant function analysis, based on a categorisation of the populations, and demonstrate how this can enhance our understanding. Our findings suggest that different aspects of the bilingual experience contribute differently to language development, regardless of language combination and type of skill measured. Contrary to what previous research suggests, measures relating to the intensity of informal use of both the L1 and the L2 in daily life are important in determining whether someone is a good or a poor L1 maintainer, while high vs. low success in acquisition appears to be predominantly associated with personal factors such as educational level.

Hemodilution is not the only reason of difference: Comparison of fasting and non-fasting lipoproteins in paired samples.

INTRODUCTION: Low-density lipoprotein cholesterol (LDL) is an important risk factor for cardiovascular disease (CVD) and generally measured after 8-12 h fasting. However, some recent studies have pointed that non-fasting lipoproteins, especially LDL concentrations, are better indicators for demonstrating CVD risk and atherosclerosis. They asserted that nutrition is a negligible factor on changes in lipoprotein concentrations and claimed this difference as a result of hemodilution effect, caused from fluid intake and can be eliminated by applying some adjustments. We aimed to compare the fasting and non-fasting LDL values of the same individuals and discuss whether non-fasting and fasting LDL results can be used in place of each other, directly or after applying hemodilution correction models. MATERIAL AND METHODS: Fasting and non-fasting blood samples of 248 apparently healthy participants were collected. Lipid panel tests, albumin and hemoglobin levels were studied in each sample. Results were evaluated in seven different models which were recommended to correct the hemodilution effect on fasting and non-fasting lipid concentrations of the same individual. Concordance of fasting and non-fasting risk group of the individual were calculated according to the National Cholesterol Education Program classification. RESULTS: Fasting and non-fasting LDL and non-high density lipoprotein cholesterol (non-HDL) concentrations were significantly different in every model (p < 0.001). Concordance results of fasting and non-fasting LDL and non-HDL risk groups were 63.8% and 77.9% respectively. CONCLUSIONS: Our results demonstrated that fasting and non-fasting LDL and non-HDL concentrations could not be used in place of each other even when the results were adjusted for elimination of the hemodilution effect.

Comparison of noninvasive and invasive point-of-care testing methods with reference method for hemoglobin measurement.

BACKGROUND: Rapid and practical point-of-care testing (POCT) devices become more popular, especially in blood donation centers for determining predonation hemoglobin (Hb) concentrations. The purpose of this study was to evaluate accordance between the POCT methods and the venous method as the reference to Hb screening. METHODS: A total of 353 subjects with no known significant health problems were included in the study. Hb screening was performed by two different POCT methods, a noninvasive method (Haemospect, MBR, Germany) and an invasive method (HemoControl, EKF Diagnostic, Germany), and a venous method as the reference (Sysmex XE-2100, Sysmex Europe, Germany). The obtained results were compared. RESULTS: The sensitivity and the specificity values of the invasive POCT method (83.3%, 87.9%) were higher than the noninvasive POCT method (66.7%, 77.1%). The Bland-Altman analysis was evaluated for both sexes and the bias of the noninvasive POCT method of the males (-0.97 g/dL) was higher than the bias of the invasive POCT method of the males (-0.07 g/dL). We found a better correlation between the invasive POCT method (r = .908) compared with the venous method than the noninvasive POCT method (r = .634). CONCLUSION: Predonation Hb measurements must be performed with accurate, precise, and practical methods. Although the noninvasive POCT method was practical and painless, it had lower levels of specificity and sensitivity, and more false deferral and pass rates than the invasive POCT method. The POCT methods agreeable to the venous method as the reference might be suitable for Hb screening especially for centers of excessive numbers of blood donation.

Transfer of single dose of intravitreal injection of ranibizumab and bevacizumab into milk of sheep.

AIM: To investigate whether single-dose intravitreal injections of bevacizumab and ranibizumab transfer into milk. METHODS: This study included lactating 12 sheep and a single 3-month old suckling lamb of each sheep. Two groups consisting of 6 sheep and their lambs were constituted; the ranibizumab group and the bevacizumab group before the administration of intravitreal injections, blood and milk samples were obtained from all sheep and, following the injections, blood and milk samples of all sheep and blood samples of all lambs were collected at regular time points. Serum and milk concentrations of bevacizumab and ranibizumab were measured using an enzyme-linked immunosorbent assay (ELISA) kit. The limit of determination was 0.9 ng/mL for bevacizumab and 0.62 ng/mL for ranibizumab. RESULTS: At 6h after intravitreal injections, bevacizumab concentration was above the limit of determination in the blood of all sheep. At 3wk, when the study was terminated, bevacizumab concentrations were high in 4 sheep. Even though bevacizumab concentrations in milk showed fluctuations, the drug transferred into the milk of all sheep at detectable concentrations. Ranibizumab drug concentrations in the blood and milk of sheep and those in the blood of lambs were below the limit of determination by the ELISA kit. CONCLUSION: This sheep model study demonstrate that intravitreal injection of ranibizumab, which did not transfer into the milk of sheep and suckling lambs, is safer than bevacizumab during lactation period.

Is Turkish MEFV Mutations Spectrum Different Among Regions?

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive inherited inflammatory disease. The gene responsible for the disease, called MEFV, encodes a protein called pyrin or marenostrin. According to recent data, MEFV mutations are not the only cause of FMF, but genetic analysis of MEFV gene is needed for confirming the diagnosis of FMF. In the present study, we aimed to evaluate the molecular testing results of MEFV mutations. METHODS: Molecular testing results of 1,435 patients were retrospectively evaluated over the last 4 years. These patients were identified as having FMF clinical symptoms. Patients were tested for 12 common mutations in the MEFV gene using a strip assay technique. RESULTS: From all 1,435 patients, MEFV mutations were found in 776 patients (54.08%) and 659 patients (45.92%) did not carry any mutations. Patients with mutations were classified as homozygotes (n = 148), compound heterozygotes (n = 197), heterozygous (n = 427), and complex genotypes (n = 4, patients with three mutations). Allelic frequencies for the four most common mutations in the mutation-positive groups were 48.79% (M694V), 14.86% (M680I G/C), 13.70% (E148Q), and 12.35% (V726A). The remaining alleles (10.3%) showed rare mutations that were R761H, P369S, A744S, K695R, F479L, and M694I. No patient showed a I692del mutation that is sometimes evident in other Mediterranean populations. CONCLUSION: It was found that the most common four mutations (M694V, M680I [G/C], E148Q, V726A) were similar to those previously reported from different regions of Turkey and this study might add some knowledge to the mutational spectrum data on FMF.

Effect of povidone iodine on thyroid functions and urine iodine levels in caesarean operations.

OBJECTIVE: In the present study, the effects of povidone iodine (PI) used during Caesarean operations on maternal thyroid hormones and urine iodine levels in the infant and the mother were investigated. DESIGN: Twenty-seven patients were allocated to the PI group I (Gr I), and 28 to the non-PI group (Group II). Maternal preoperative and 24th-h postoperative free T3 (fT3), freeT4 (fT4), TSH, and urine iodine levels were determined, as well as infant urine iodine values. RESULTS: In both groups, fT3 levels before and after the operation were found to be reduced (p < 0.01, p = 0.01, respectively). However, the decrease in fT3 was approximately 1.5-fold higher in Gr I than in Gr II. TSH levels increased significantly in Gr I (p = 0.005). The urine iodine levels of the mothers increased 25% in Gr I, but only 2% in Gr II. CONCLUSIONS: The absorption of PI by the skin was found to lead to changes in fT3, TSH, and urine iodine excretion values in the mothers. The findings of this study of Caesarean operations, which have a short duration, might be a signal to be careful of thyroid hormone effects in operations lasting longer.