Current clinical practice and needs assessment in inherited eye diseases from the perspective of ophthalmologists.

BACKGROUND: The clinical approach to inherited eye diseases has evolved due to advances in genetic testing methods and treatment opportunities. However, no data are available on the current practices of ophthalmologists in countries, such as Turkey, with higher rates of consanguinity and inherited eye diseases. The aim of this study was to evaluate the current practices, knowledge, and needs of ophthalmologists in Turkey regarding inherited eye diseases. METHODS: A 29-item self-administered survey with a branching algorithm was developed through Google Forms. The survey link was sent to 2983 ophthalmologists in Turkey. The survey assessed respondents' occupational characteristics, current practices, knowledge about available diagnostic and therapeutic options, and opinions on improving continuing education and healthcare services. RESULTS: Responses from 414 ophthalmologists (20.8%) were analyzed. The responses suggested that ophthalmologists mainly collaborate with medical geneticists in respect of inherited eye diseases. The majority of ophthalmologists reported a lack of knowledge about genetic diagnostic tests, and approximately 90% of the ophthalmologists thought training after residency was inadequate for inherited eye diseases. CONCLUSION: This is the most extensive survey exploring ophthalmologists' practice patterns and needs in a setting without specialists or specialized centers in ophthalmic genetics. The results emphasize the need for continued education on updated approaches to inherited eye diseases.

Significance of intestinal alkaline phosphatase in predicting histological activity of pediatric inflammatory bowel disease.

BACKGROUND: Intestinal alkaline phosphatase (iAP) is an intestinal brush border enzyme that is one of the factors involved in the pathogenesis of inflammatory bowel disease (IBD). The aim of the study was to investigate the relationship between iAP enzyme and histological inflammatory activity in patients with IBD. METHODS: A total of 44 children were enrolled in this study including IBD patients (n=24; 12 Crohn`s disease [CD] and 12 ulcerative colitis [UC]) and controls (n=20). Anti-human iAP antibody stained ileocolonoscopic biopsy specimens were graded for the terminal ileum and each section of the colon. Hematoxylin-eosin stained sections were used to determine inflammatory activity. Histopathological findings were compared in pre- and post-treatment biopsies of each group and with the control group (CG). RESULTS: A low grade of iAP staining was detected in IBD patients compared to the CG (p=0.02). iAP was remarkably concentrated in the terminal ileum (TI) and especially in region 1, which involved the apical surface, brush border, and epithelial cells. A significant negative correlation was found between the grade of iAP staining and inflammatory activity both in pre- and post-treatment biopsies (p=0.02, p=0.008, respectively) in the terminal ileum of CD patients. Likewise, pre-treatment biopsies of UC and CD patients and biopsies of the CG were compared with each other according to the grade of iAP staining. There were significant negative correlations for CD patients compared to UC and the CG in region1 of TI, and regions 1 and 2 (lamina propria and goblet cells) of the colon (p= 0.015, p= 0.006, p < 0.001, respectively). CONCLUSIONS: As a histological marker, iAP can be of value in monitoring the histological activity of IBD, particularly in remarkable inflammation in the small intestine.

Status and trends of personalized medicine research from 2000 to 2020: a bibliometric analysis.

BACKGROUND: Personalized medicine (PM), as a rapidly growing research area, provides treatments, practices, and interventions being adapted to an individual patient based on his own risk of disease. This study aims to analyze the productivity of countries, institutions, and authors in this field, to determine the existing research trends worldwide, and to forecast future research activity for specific countries. METHODS: Documents published between 2000 and 2020 were retrieved from the Web of Science (WoS) database. Bibliometric analysis was performed to assess the outputs, correlation analysis was applied to analyze the relationship between Gross Domestic Product per capita (GDP-PP) and the number of publications, and an extrapolation method was used for predicting the future productivity trends for certain countries. RESULTS: A total of 7,772 documents were published globally on PM between 2000 and 2020. The most productive country, journal, and institution are the USA, Personalized Medicine, and Harvard Medical School, respectively. The USA is also first in line in terms of total citations. Netherlands, Denmark, and the USA are listed at the top in terms of the total number of papers and citations, after adjusting for GDP-PP and population size. Also, as predictions suggest, the USA will maintain its predominant role in the PM field in the next 5 years. CONCLUSIONS: Owing to its both interdisciplinary and multidisciplinary nature, PM bestows researchers' numerous sources to benefit and enables them a field that they can be productive of for the future. Therefore, this field is expected to progress and be the lead area in medicine in the upcoming years.

Patterns of Post-Endodontic Restoration: A Nationwide Survey of Dentists in Turkey.

Developments in materials and techniques, geographical locations, age, specialty, and affiliations of dental practitioners affect the preference of post-endodontic restoration. Thus, this survey aimed to evaluate the trends of dentists in Turkey in terms of post-endodontic restorations. An anonymous survey containing 10 questions regarding demographics, post-endodontic restoration patterns, and factors affecting restoration selection was electronically delivered to the dentists registered in the database of the Turkish Dental Association. The data were analyzed using by a chi-square test and ordinal logistic regression analysis. A total of 1093 surveys from 20,564 participants were collected with a response rate of 5.3%. Half of the participants (52%) preferred composite resins for post-endodontic restorations. Usage of posts was less prevalent amongst prosthodontists and dentists with clinical experience of more than 20 years compared to endodontists (p < 0.001) and dentists with clinical experience of less than 5 years (p = 0.004). More than half of the participants (56%) utilized fiber posts. Composite resins and fiber posts were the most common preferences in post-endodontic restoration. Endodontists had a higher tendency to use posts than prosthodontists and general dental practitioners.

Antibacterial Effect and Bioactivity of Innovative and Currently Used Intracanal Medicaments in Regenerative Endodontics.

INTRODUCTION: The purpose of this study was to determine the antibacterial effect and bioactivity of triple antibiotic paste (TAP), calcium hydroxide (Ca[OH]2), and calcium hypochlorite (Ca[OCl]2). METHODS: Root canals were infected with 3-week-old Enterococcus faecalis biofilm and then medicated for 7 days with TAP, Ca(OH)2, or Ca(OCl)2 (n = 10/group). Untreated and uninfected canals were used as positive and negative controls. The antibacterial effect was determined using colony-forming units and a Live/Dead bacterial viability kit. Dental pulp stem cells were seeded on medicated dentin surfaces for 7 days. Sodium thiosulfate and various concentrations of ascorbic acid (1%, 5%, and 10%) were also used to neutralize the samples treated with Ca(OCl)2 before cell seeding (n = 3 in triplicate). Cell viability and morphology were evaluated using a viability assay and Live/Dead cell analysis. Alkaline phosphatase (ALP) activity was also measured to determine the cells' mineralization activity. RESULTS: All medicaments decreased the initial bacterial load (P < .05). The highest bacterial reduction in the main canal and dentinal tubules was observed in the Ca(OCl)2 group (P < .05). TAP- or Ca(OH)2-treated dentin surface improved cell viability and ALP activity compared with the untreated dentin surface (P < .05), whereas Ca(OCl)2 decreased cell viability and ALP activity (P < .05). Ten percent ascorbic acid neutralized the effect of Ca(OCl)2 on the treated dentin surface, showing higher cell viability (P < .05) and similar ALP activity with the untreated dentin surface and the other groups (P > .05). CONCLUSIONS: Ca(OCl)2 medication improved root canal disinfection against E. faecalis biofilm compared with TAP and Ca(OH)2. The adverse effects caused by Ca(OCl)2 on cell viability and mineralization activity can be neutralized with 10% ascorbic acid.

Disease severity and poor mental health are the main predictors of stigmatization in patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) causes significant psychological distress in patients. We aimed to investigate the stigmatization level of HS patients and to determine the related physical, social, and psychological factors. A questionnaire with 22 questions about the physical and psychosocial problems related to HS was administered to 29 male and 34 female patients between the ages of 18 and 66 to evaluate the thoughts, emotions, attitudes, and behaviors of patients. Each patient filled Dermatology Life Quality Index, Beck Depression Inventory, Liebowitz Social Anxiety Scale, Body Image Scale, and 6-item Stigmatization Scale. Hurley classification was used to assess severity of disease. Patients with HS feel stigmatized depending on physical and psychosocial problems caused by the disease. Higher stigmatization scores correlated with higher scores of depression (r: .437, P < .001), social anxiety (r: .263, P: .03), and worse life quality (r: .522, P < .001), and body image perception (r: .696, P < .001). The degree of stigmatization was closely associated with the presence of painful lesions and disruption of socializing (P: .021 and .033, respectively). Disease severity (ß: 5.12, P: .003 for moderate disease) and reporting feeling psychologically negatively affected due to HS (ß: 4.26 P: .007) were the two main predictors of stigmatization in patients with HS. Cross-sectional nature of the study is the limitation. In conclusion, the stigmatization level of patients with HS is strongly related to disease severity and poor mental health.

Two novel nomograms for predicting the risk of hospitalization or mortality due to COVID-19 by the naïve Bayesian classifier method.

Coronavirus disease 2019 (COVID-19) has become a global pandemic that has affected millions of people worldwide. The presence of multiple risk factors for COVID-19 makes it difficult to plan treatment and optimize the use of medical resources. The aim of this study is to determine potential risk factors for hospitalization or mortality in patients with COVID-19 via two novel naive Bayesian nomograms. The publicly available COVID-19 National data published by the Mexican Ministry of Health through the "Dirección General de Epidemiología" website was analyzed. Univariable logistic regression was utilized to identify potential risk factors that may affect hospitalization or mortality in patients with COVID-19. The naïve Bayesian classifier method was implemented to predict nomograms. The nomograms were verified by the area under the receiver operating characteristic curve (AUC), classification accuracy (CA), F1 score, precision, recall, and calibration plot. A total of 979,430 patients (45.3 ± 15.9 years old, and 51.1% male) tested positive for COVID-19 from January 1 to November 22, 2020. Among them, 22.3% of the patients required hospitalization and 99,964 patients (9.8%) died. The most important risk factors to predict the probability of hospitalization and mortality were pneumonia, age, chronic kidney failure, chronic obstructive respiratory disease, and diabetes. The performance measures demonstrated good discrimination and calibration (hospitalization: AUC = 0.896, CA = 0.880; mortality: AUC = 0.903, CA = 0.899). Two novel nomograms to estimate the risk of hospitalization and mortality were proposed, which could be used to facilitate individualized decision-making for patients newly diagnosed with COVID-19.

Joint Modeling Approach on Evaluating Time-Dependent CutOff Values for C-Reactive Protein in Mixed Intensive Care Unit Population.

BACKGROUND: Serial C-reactive protein (CRP) biomarker values are frequently recorded from patients in adult intensive care units (ICU). The aim of this study was to assess the time-dependent diagnostic accuracy of repeated CRP measurements in predicting ICU mortality and determine the time-dependent cutoff values for this biomarker in mixed ICU population. METHODS: Joint modeling was performed to model repeated CRP measurements and survival data. Time-dependent AUC (td-AUC) values were used to assess the diagnostic performances. Maximization of the product of sensitivity and specificity rule was applied to determine the time-dependent cutoff values. RESULTS: Time-dependent diagnostic performance of serial CRP values were found as moderate in overall, observed to be higher in males than females, ranging from 0.603 to 0.624 in females and 0.639 to 0.690 in males. On the other hand, time-dependent cutoff values either remained constant or decreased through the 3rd day after the last measurement for both gender groups. CONCLUSIONS: Newly proposed time-dependent cutoff values for CRP biomarker are suggested to be used in clinics to discriminate subjects who are at risk and who are not during the first three days after the last measurement. Furthermore, taking serial CRP values in predicting the risk of death at ICU is highly recommended, to be able to assess the change in longitudinal profiles of subjects throughout the follow-up period.

Association between benign prostate enlargement-related storage and voiding symptoms and systolic blood pressure: a single-center cross-sectional study

ABSTRACT BACKGROUND: Lower urinary tract symptoms significantly worsen quality of life. The hypothesis that they might lead to serious systolic blood pressure alterations through inducing sympathetic nervous activity has not been studied so far. OBJECTIVES: To investigate the relationship between benign prostate enlargement-related storage and voiding symptoms and systolic blood pressure. DESIGN AND SETTING: Cross-sectional single-center study on data from a hospital patient record system. METHODS: We evaluated the medical records of all consecutive patients with benign prostate enlargement-related lower urinary tract symptoms admitted between January 2012 and December 2017. Storage and voiding symptoms were assessed separately. International Prostate Symptom Score, uroflowmetry, postvoiding residual urine volume and systolic blood pressure were recorded. Pearson correlation and linear regression analysis were used. RESULTS: Positive correlations were found between systolic blood pressure and all of the storage symptoms. Among these, urgency had the most significant effect. There were 166 patients (41.4%) with urgency for urination, which increased mean systolic blood pressure from 124.88 mmHg (average value in elevated blood pressure group) to 132.28 mmHg (average value in stage-1 hypertension group). Hesitancy in urinating and feeling of incomplete bladder emptying had weak positive correlations with systolic blood pressure. There was a negative correlation between systolic blood pressure and intermittency of urination. CONCLUSIONS: With increasing numbers of urine storage symptoms, systolic blood pressure also increases, while the opposite occurs for voiding symptoms in patients with benign prostate enlargement. We conjecture that storage symptoms may lead to this increase through inducing sympathetic hyperactivity. Further prospective studies with larger groups are needed to confirm these findings.

Association between benign prostate enlargement-related storage and voiding symptoms and systolic blood pressure: a single-center cross-sectional study.

BACKGROUND: Lower urinary tract symptoms significantly worsen quality of life. The hypothesis that they might lead to serious systolic blood pressure alterations through inducing sympathetic nervous activity has not been studied so far. OBJECTIVES: To investigate the relationship between benign prostate enlargement-related storage and voiding symptoms and systolic blood pressure. DESIGN AND SETTING: Cross-sectional single-center study on data from a hospital patient record system. METHODS: We evaluated the medical records of all consecutive patients with benign prostate enlargement-related lower urinary tract symptoms admitted between January 2012 and December 2017. Storage and voiding symptoms were assessed separately. International Prostate Symptom Score, uroflowmetry, postvoiding residual urine volume and systolic blood pressure were recorded. Pearson correlation and linear regression analysis were used. RESULTS: Positive correlations were found between systolic blood pressure and all of the storage symptoms. Among these, urgency had the most significant effect. There were 166 patients (41.4%) with urgency for urination, which increased mean systolic blood pressure from 124.88 mmHg (average value in elevated blood pressure group) to 132.28 mmHg (average value in stage-1 hypertension group). Hesitancy in urinating and feeling of incomplete bladder emptying had weak positive correlations with systolic blood pressure. There was a negative correlation between systolic blood pressure and intermittency of urination. CONCLUSIONS: With increasing numbers of urine storage symptoms, systolic blood pressure also increases, while the opposite occurs for voiding symptoms in patients with benign prostate enlargement. We conjecture that storage symptoms may lead to this increase through inducing sympathetic hyperactivity. Further prospective studies with larger groups are needed to confirm these findings.

Is Magnetically Controlled Growing Rod the Game Changer in Early-onset Scoliosis? A Preliminary Report.

BACKGROUND: Magnetically controlled growing rod (MCGR) concept was introduced with the premise of minimizing the repetitive lengthening surgeries, which is default in traditional growing rod (TGR) treatment for early-onset scoliosis (EOS). Despite good radiographic outcomes, previous studies did not compare identical patient groups in terms of etiology and deformity characteristics; therefore, a true comparison of the MCGR and TGR is essential. This study was designed to compare 2 techniques in terms of clinical, radiologic, and health-related quality of life (HRQoL) outcomes. METHODS: Patients with long sweeping congenital curves who underwent convex growth arrest and concave distraction (with TGR or MCGR) were retrospectively reviewed. Instrumented all-posterior convex growth arrest and concave distraction with growing rod technique were performed. Demographic parameters, follow-up time, number of lengthening procedures, radiographic parameters, number of unplanned surgeries, and complications were recorded. The Early-Onset Scoliosis Questionnaire (EOSQ-24) was used to evaluate HRQoL outcomes. RESULTS: A total of 20 patients were included (10 MCGR, 10 TGR). No significant differences were found with regard to average age, follow-up time, radiographic parameters, or complications. Overall surgery per patient including index surgery, and planned and unplanned procedures were significantly lower in the MCGR group (8.8 vs. 1.3) (P=0.01). No patient in either group had graduated from growing rod treatment. HRQoL analysis revealed no significant difference between the 2 groups in any specific domain or in the overall score of the EOSQ-24. CONCLUSIONS: Although equally effective in controlling the deformity and superior in reducing the number of surgeries with comparable complication rates, MCGR does not offer any significant improvement in HRQoL outcomes or the overall complication rate. Despite the obvious advantages, according to this preliminary report, the current technology and technique of MCGR may not be sufficient to be the long-awaited "game changer" in the treatment of EOS.

Surface and vertical dimensional changes of mineral trioxide aggregate and biodentine in different environmental conditions.

OBJECTIVES: Surface changes in biological environments are critical for the evaluation of physical and biological activity of biomaterials. Objective: This study investigated surface alterations of calcium silicate-based cements after exposure to different environments. MATERIAL AND METHODS: Material and Methods: Forty-eight cylindrical cavities were prepared on root surfaces. The cavities were filled using ProRoot MTA or Biodentine and assigned to four subgroups (n=6): dry, wet, acidic, and blood. Surface topographies were evaluated using an optical profilometer for 28 days, and the roughness of the material surfaces was quantified. Vertical dimensional change was measured by determining the height difference between the material surface and the flat tooth surface. Data were compared with a two-way repeated measures ANOVA and Bonferroni tests. RESULTS: Results: In dry condition, the surface roughness of MTA or Biodentine was constant up to 3 days (p>0.05) but decreased after 28 days (p<0.05). In dry condition, ProRoot MTA presented constant surface level through time, while Biodentine showed decreased surface level after 28 days. In wet condition, the roughness and the surface levels of both materials increased after 1 day (p<0.05). Neither the surface roughness nor the levels of the materials showed significant changes in acidic conditions (p>0.05). Both materials showed the highest roughness in blood conditions on the 1st day (p<0.05), while the surface roughness in blood decreased dramatically after 28 days. The roughness of Biodentine was higher in wet conditions up to 3 days compared with ProRoot MTA (p<0.05). Likewise, in blood condition, Biodentine showed higher roughness on the 28th day than ProRoot MTA (p<0.05). CONCLUSIONS: Conclusions: Dry, wet, and blood conditions had a time-dependent effect on the surface roughness and vertical dimensional changes of the materials. However, acidic conditions did not affect the roughness and the surface level of the materials.

Plasma Thiol Levels are Associated with Disease Severity in Nonsegmental Vitiligo.

BACKGROUND: Vitiligo is a depigmenting cutaneous disorder with complex pathogenesis. Thiol compounds are well-known organic structures that play a major role in melanogenesis. AIM: The aim of this study was to determine the association between plasma thiol level and disease severity in patients with nonsegmental vitiligo. METHODS: A total of 73 patients with nonsegmental vitiligo (57 generalized and 16 localized type) and age- and sex-matched 69 healthy controls were enrolled in the study. Plasma levels of native thiols, disulfides, and total thiols were measured by a novel and automated assay. Disease severity of vitiligo was assessed with Vitiligo Area Scoring Index (VASI) score. The extent, stage, and spread of vitiligo of patients were evaluated according to the Vitiligo European Task Force (VETF) system. RESULTS: The native and total thiol levels of vitiligo patients were higher than those of healthy control group (P≤0.001 and 0.001, respectively). The median VASI score of patients was 0.7 (0.02-28.30). Univariate analyses showed that plasma native thiol levels, VETF spread score, disease duration, and vitiligo type significantly correlated with VASI scores (r=0.237, P=0.043; r=0.458, P<0.001; and P<0.001, respectively). Stepwise multivariate analysis revealed that disease duration (ß=0.017; P=0.005) and spread score (ß=1.301; P=0.001) were found statistically significant as independent factors on VASI score. CONCLUSION: Although plasma native thiol level significantly correlated with VASI scores of patients, it is not a predictive factor for vitiligo severity.

A statistical approach to evaluate the performance of cardiac biomarkers in predicting death due to acute myocardial infarction: time-dependent ROC curve

Background/aim: Myoglobin, cardiac troponin T, B-type natriuretic peptide (BNP), and creatine kinase isoenzyme MB (CK-MB) are frequently used biomarkers for evaluating risk of patients admitted to an emergency department with chest pain. Recently, time- dependent receiver operating characteristic (ROC) analysis has been used to evaluate the predictive power of biomarkers where disease status can change over time. We aimed to determine the best set of biomarkers that estimate cardiac death during follow-up time. We also obtained optimal cut-off values of these biomarkers, which differentiates between patients with and without risk of death. A web tool was developed to estimate time intervals in risk. Materials and methods: A total of 410 patients admitted to the emergency department with chest pain and shortness of breath were included. Cox regression analysis was used to determine an optimal set of biomarkers that can be used for estimating cardiac death and to combine the significant biomarkers. Time-dependent ROC analysis was performed for evaluating performances of significant biomarkers and a combined biomarker during 240 h. The bootstrap method was used to compare statistical significance and the Youden index was used to determine optimal cut-off values. Results : Myoglobin and BNP were significant by multivariate Cox regression analysis. Areas under the time-dependent ROC curves of myoglobin and BNP were about 0.80 during 240 h, and that of the combined biomarker (myoglobin + BNP) increased to 0.90 during the first 180 h. Conclusion: Although myoglobin is not clinically specific to a cardiac event, in our study both myoglobin and BNP were found to be statistically significant for estimating cardiac death. Using this combined biomarker may increase the power of prediction. Our web tool can be useful for evaluating the risk status of new patients and helping clinicians in making decisions.

Receptor for advanced glycation end products is overexpressed in psoriatic plaques independent of disease severity.

BACKGROUND: Enhanced expression and excitation of the receptor for advanced glycation end products is considered to play a role in the regulation of many pro-inflammatory genes involved in the pathogenesis of psoriasis. AIM: We investigated the expression of receptor for advanced glycation end product in various cell types, in lesional and peri-lesional skin of patients with psoriasis, and its correlation with disease severity. METHODS: Paraffin-embedded punch biopsy tissue taken from psoriatic plaques and peri-lesional normal appearing skin tissue of twenty patients with psoriasis, and normal skin samples of eleven healthy participants, were enrolled in the study. The sections were stained immunohistochemically with anti-receptor for advanced glycation end product antibody. The intensity of receptor for advanced glycation end product expression was assessed semi-quantitatively on epidermal cells, microvascular endothelium, dermal fibroblasts and inflammatory cells. They were graded as follows: 0 (no staining), 1 (weak), 2 (moderate) and 3 (strong) intensity. RESULTS: Receptor for advanced glycation end product expression on epidermis, microvascular endothelium, inflammatory cells and fibroblasts in the psoriatic plaques was more intense than perilesional and normal tissue (all P < 0.05). It did not correlate with disease severity. LIMITATIONS: The main limitation of our study is that this was a semi-quantitative assessment, detected immunohistochemically in skin biopsies. CONCLUSION: Receptor for advanced glycation end product expression may have an important role in psoriasis pathogenesis, independent of disease severity.

Expression of the receptor for advanced glycation end products in acquired reactive perforating collagenosis.

BACKGROUND: Acquired reactive perforating collagenosis (ARPC) is a rare skin disorder characterized by transepidermal elimination of dermal collagen. There is little data regarding the pathogenesis of ARPC. The receptor for advanced glycation end products (RAGE) is a multiligand transmembrane receptor that plays an important role in inflammatory responses and may be involved in the pathogenesis of ARPC. AIM: To explore the expression of RAGE in ARPC. METHODS: Paraffin-embedded punch biopsy specimens of 41 patients with ARPC and of 11 healthy controls with normal skin were obtained from the Department Of Pathology. Clinical data of all patients were reviewed from the medical files. All specimens were stained immunohistochemically with antibody to RAGE (Anti-RAGE). The intensity of RAGE expression was assessed semi-quantitatively on epidermal cells, microvascular endothelium, dermal fibroblasts and inflammatory cells and graded as 0 (no staining), 1 (weak), 2 (moderate) and 3 (strong). The patients were divided into diabetic and nondiabetic groups for analysis. RESULTS: RAGE expression in microvascular endothelium, inflammatory cells and fibroblasts of patients with ARPC was more intense than normal tissues of healthy participants (P values are 0.005, 0.017 and P > 0.05). LIMITATIONS: Our method of assessment of RAGE expression was semi-quantitative. CONCLUSION: We observed an overexpression of RAGE in lesional samples of patients with ARPC which was independent of the presence of diabetes.

Endocannabinoids modulate apoptosis in endometriosis and adenomyosis.

Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues. Findings were compared to normal endometrium and myometrium. Endometrial adenocarcinoma (Ishikawa) and ovarian endometriosis cyst wall stromal (CRL-7566) cell lines were furthermore cultured with or without cannabinoid receptor agonists. The IC50 value for CB1 and CB2 receptor agonists was quantified. Cannabinoid agonists on cell death were investigated by Annexin-V/Propidium iodide labeling with flow cytometry. CB1 and CB2 receptor levels decreased in endometriotic and adenomyotic tissues compared to the control group (p=0,001 and p=0,001). FAAH, NAPE-PLD, MAGL and DAGL enzyme levels decreased in endometriotic and adenomyotic tissues compared to control (p=0,001, p=0,001, p=0,001 and p=0,002 respectively). Apoptotic cell indexes both in endometriotic and adenomyotic tissues also decreased significantly, compared to the control group (p=0,001 and p=0,001). CB1 and CB2 receptor agonist mediated dose dependent fast anti-proliferative and pro-apoptotic effects were detected in Ishikawa and ovarian endometriosis cyst wall stromal cell lines (CRL-7566). Endocannabinoids are suggested to increase apoptosis mechanisms in endometriosis and adenomyosis. CB1 and CB2 antagonists can be considered as potential medical therapeutic agents for endometriosis and adenomyosis.

The serum angiotensin converting enzyme and lysozyme levels in patients with ocular involvement of autoimmune and infectious diseases.

BACKGROUND: Increased serum levels of angiotensin converting enzyme and lysozyme are considered as inflammatory markers for diagnosis of sarcoidosis which is an autoimmune inflammatory disease. The purpose of this study is to evaluate the significance of differences in serum angiotensin converting enzyme and lysozyme levels of patients with ocular involvement of other autoimmune inflammatory and infectious diseases. METHODS: This is a prospective study involving patients with ankylosing spondylitis, behcet's disease, presumed sarcoidosis, presumed latent tuberculosis, presumed latent syphilis, and control group. The serum levels of angiotensin converting enzyme and lysozyme were analyzed by enzyme-linked immunosorbent assay. Bonnferoni analysis was used to assess pairwise comparisons between the groups. RESULTS: There was a significant increase in serum angiotensin converting enzyme level in patients with presumed sarcoidosis compared to ankylosing spondylitis (p = 0.0001), behcet's disease (p = 0.0001), presumed latent tuberculosis (p = 0.0001), presumed latent syphilis (p = 0.0001), and control group (p = 0.0001). The increase in serum lysozyme level was significant for patients with presumed sarcoidosis with respect to ankylosing spondylitis (p = 0.0001), behcet's disease, (p = 0.0001) presumed latent tuberculosis (p = 0.001), presumed latent syphilis (p = 0.033), and control group (p = 0.0001). CONCLUSION: Elevated serum angiotensin converting enzyme levels are significant for patients with presumed sarcoidosis compared to ocular involvement of other autoimmune diseases such as behcet's disease and ankylosing spondylitis, and ocular involvement of infectious diseases such as presumed latent tuberculosis and presumed latent syphilis. However, elevated serum lysozyme level might be also detected in ocular involvement of infectious diseases such as presumed latent tuberculosis and presumed latent syphilis. TRIAL REGISTRATION NUMBER: NCT02627209. Date of registration: 12/09/2015.

Gestation specific reference intervals for thyroid function tests in pregnancy.

BACKGROUND: Thyroid function tests are frequently assessed during pregnancy to evaluate thyroid dysfunction or to monitor pre-existing thyroid disease. However, using non-pregnant reference intervals can lead to misclassification. International guidelines recommended that institutions should calculate their own pregnancy-specific reference intervals for free thyroxine (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH). The objective of this study is to establish gestation-specific reference intervals (GRIs) for thyroid function tests in pregnant Turkish women and to compare these with the age-matched non-pregnant women. METHODS: Serum samples were collected from 220 non-pregnant women (age: 18-48), and 2460 pregnant women (age: 18-45) with 945 (39%) in the first trimester, 1120 (45%) in the second trimester, and 395 (16%) in the third trimester. TSH, FT4 and FT3 were measured using the Abbott Architect i2000SR analyzer. RESULTS: GRIs of TSH, FT4 and FT3 for first trimester pregnancies were 0.49-2.33 mIU/L, 10.30-18.11 pmol/L and 3.80-5.81 pmol/L, respectively. GRIs for second trimester pregnancies were 0.51-3.44 mIU/L, 10.30-18.15 pmol/L and 3.69-5.90 pmol/L. GRIs for third trimester pregnancies were 0.58-4.31 mIU/L, 10.30-17.89 pmol/L and 3.67-5.81 pmol/L. GRIs for TSH, FT4 and FT3 were different from non-pregnant normal reference intervals. CONCLUSIONS: TSH levels showed an increasing trend from the first trimester to the third trimester, whereas both FT4 and FT3 levels were uniform throughout gestation. GRIs may help in the diagnosis and appropriate management of thyroid dysfunction during pregnancy which will prevent both maternal and fetal complications.

The association of vitamin D, cathelicidin, and vitamin D binding protein with acute asthma attacks in children.

BACKGROUND: Recent evidence about the various effects of vitamin D (vit D) on innate and adaptive immunity has led to a search for the role of vit D in asthma. It is postulated that a decrease in cathelicidin, a multifunctional host defense molecule, production due to low vit D status may predispose to infectious complications in children with asthma. OBJECTIVE: The aim of this study was to determine the association of vit D, vit D-binding protein (VDBP) and cathelicidin with acute asthma attacks among children with allergic asthma. METHODS: This prospective study included 35 patients with acute asthma attack and 32 children with controlled asthma, and all were matched by sampling season, sensitization to mites, and previous severity of asthma. A comprehensive questionnaire about risk factors, blood sampling for 25-hydroxyvitamin D vit D, VDBP, and cathelicidin levels; spirometric indices were used. Factors that influence serum vit D and cathelicidin levels and the development of asthma attacks were evaluated with multivariate analysis. RESULTS: The mean serum vit D levels of the attack group was significantly lower than that of the controlled asthma group (p < 0.001). The mean cathelicidin level was significantly higher in the acute asthma group than with the controlled subjects with asthma (p = 0.002). There was no difference between the acute and controlled asthma groups in terms of markers of allergy and serum VDBP levels. Risk factors that may influence vit D levels revealed that body mass index (BMI) (p = 0.038), duration of sun exposure (p < 0.001), and amount of dietary vit D (p < 0.001) independently affected serum vit D levels. Risk factors that may result in acute asthma showed that low serum levels of vit D were significantly related to the risk of asthma attacks (p < 0.001, adjusted odds ratio 16.11). Cathelicidin levels showed a significant positive association with asthma attacks and BMI. CONCLUSIONS: Vit D deficiency showed a significant relationship to the development of asthma attacks independent of cathelicidin deficiency and other factors associated with the severity of chronic asthma.