Delays in Newborn Screening for Phenylketonuria from Birth to Diagnosis and Factors Affecting This.

This study aims to evaluate the process of neonatal phenylketonuria (PKU) screening from birth to admission to the pediatric metabolism polyclinic, determining delays in the screening program and the factors influencing them. This study was conducted during 2021-2023. Blood collection dates, results, and probable parameters causing delays in the screening program were recorded. This study included 118 infants. Admission time to the polyclinic was (mean ± SD) 25.2 ± 12.6 days (min-max: 3.4-78.9 days). Admission time was significantly high for refugees, those whose parents were consanguineous, and those who had more heel-prick blood samples taken (p < 0.001, p = 0.005, and p < 0.001, respectively). The first heel-prick blood phenylalanine (phe) level was significantly negatively correlated with the admission time (p < 0.001). Patients' admission time whose first blood phe level < 240 µmol/L was statistically significantly higher than in those with ≥240 µmol/L (p < 0.001). We determined that there were delays in PKU screening from birth to admission to the polyclinic. Being a refugee, the presence of consanguineous marriages, the increase in the number of heel-prick tests, and blood phe levels at a range of 120-240 µmol/L were the factors that played a role in this delay. Taking steps to reduce the impact of these parameters can prevent delays in newborn PKU screening and increase the success of the screening program.

Malar rash and hand tremor in early symptoms of cerebrotendinous xanthomatosis and the effect of chenodeoxycholic acid on them.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX, OMIM #213700) is a rare but treatable lipid storage disease resulting from mutations in the CYP27A1 gene. PURPOSE: The study aims to evaluate patients diagnosed with CTX and reveal new information, especially about the signs of CTX and patients' response to the treatment. METHODS: The study was conducted retrospectively in 12 definitively diagnosed CTX patients. The patients' clinical, laboratory, imaging, genetic findings, and chenodeoxycholic acid (CDCA) treatment results were analyzed. RESULTS: The median age at diagnosis for the patients was 16.5 years (minimum-maximum: 7-32). Juvenile cataracts, detected in more than 90% (11/12) of the patients, were the most common clinical finding. Malar rash, not previously reported in the literature for CTX, was present in 75% (9/12) of the patients. Hand tremors, the first neurological symptom, occurred in adolescence and were the initial symptom of the disease in five patients. Hand tremors were present in 83.3% (10/12) of the patients. Hand tremors (in 5 patients) and malar rash (in 2 patients) were clinical findings with full recovery due to the CDCA treatment. CONCLUSION: The study defines the malar rash finding, which has not been reported in the literature before, as a possible new clinical finding in CTX disease, attributed to its partial or full recovery with CDCA treatment. Additionally, as a novelty in the literature, our study highlights the full recovery of neurological findings, such as hand tremors, in CTX. Patients presenting with hand tremors and malar rash, especially in adolescence, should undergo CTX investigation for early diagnosis and treatment.

Histological and morphological development of the prepuce from birth to prepubertal age.

PURPOSE: To study the histological changes of the preputial tissue from birth to prepubertal age in order to define unnoticed morphological changes. MATERIALS AND METHODS: Prepuce samples were obtained from 79 healthy boys who underwent routine ritual circumcision. Specimens were divided into six groups according to the boys' age: newborn, 0-1 year of age, 2-3 years of age, 4-5 years of age, 6-7 years of age, and 8-9 years of age. Histologic analysis of the specimens was performed by H&E, Masson's trichrome, Verhoeff-Von Gieson, immunohistochemical staining. RESULTS: Microscopic examinations showed that average epithelial thickness increased after the neonatal period (p=0.001). When collagen fiber density was evaluated, no significant differences between groups were found (p=0.083). When the elastic fibers in the dermis were evaluated, it was determined that the number and thickness of elastic fibers increased with age. Immunohistochemical examinations showed that the number of peripheral nerves marked with S100 was lower in the neonatal period than at other ages (p=0.048). When the vessels marked with CD105 antibody were counted, there was no significant difference between the groups (p=0.078). CONCLUSIONS: This is the first study to examine the age-related structure of connective tissue elements in the foreskin. Our results showed that the prepuce's prepubertal maturation process is continuous, and the first 2 years of life are appropriate not only in relation to the physiological effects of age but also the optimum structural changes for wound healing, such as vessel diameter, epithelium thickness, peripheral nerve count.

Evaluation of newborn hearing screening results of infants with phenylketonuria.

OBJECTIVE: The purpose of this study is comparing the newborn hearing screening failure rate between phenylketonuria (PKU) infants and matched healthy control infants. PATIENTS AND METHODS: Between April 2021 and April 2023, data obtained from the national newborn hearing screening program were examined for patients who presented to the pediatric metabolism clinic of Konya City Hospital with a clinical and genetic diagnosis of PKU. A healthy control group, matched for age and gender, was established. The newborn hearing screening test results, demographic information, and pregnancy data of infants with PKU and the control group were compared to assess risk factors. RESULTS: In the initial screening test, 23 out of 73 PKU infants (31.5%) and 12 out of 73 infants in the control group (16.4%) failed the test (p = 0.033). Among the 23 PKU infants who did not pass the first test, 9 (35%) also failed the second test and were referred. In contrast, all 12 infants in the control group who did not pass the first test passed the second test. The failure rate in the second test was significantly higher in PKU infants compared to the control group (p = 0.003). It was observed that the maternal age of PKU infants who underwent the second test was significantly higher than that of the control group (p < 0.029). Diagnostic hearing test results were found to be normal in all nine PKU patients who failed the secondary screening test and were referred to a tertiary center. CONCLUSION: In our study, it was determined that infants with phenylketonuria (PKU) who did not have any risk factors for hearing loss failed the hearing screening test significantly more than healthy infants.

Evaluation of the effect of obesity, dietary glycemic index and metabolic profiles on the cardiovascular risk in children with classical phenylketonuria.

OBJECTIVES: To compare the glycemic index(GI),obesity,echocardiographic,and arterial stiffness measurements with the healthy control group to evaluate the cardiovascular risk of pediatric classical phenylketonuria(PKU). METHODS: The study was a prospective observational,involving 104 pediatric volunteers between 2019 and 2020.Two groups were formed:the PKU patient group and the healthy control group.These two groups were further divided into three subgroups:obese,overweight,and normal weight.The patients' anthropometric measurements,body fat analysis,biochemical analysis, GI and glycemic load(GL),arterial stiffness measurements,and echocardiographic findings were recorded. RESULTS: The PKU patient group's glucose,total cholesterol,LDL,and HDL values were significantly lower than the healthy control group(p = 0.010 for glucose and p = 0.001 for total cholesterol,LDL and HDL).Triglyceride levels were higher in the PKU patient group than in the healthy controls(109.6 vs. 76.7 mg/dl,p = 0.001). GI and GL were significantly lower in the PKU patient group than in the healthy control group(GI 453 vs. 392.9,p = 0.017 and GL 101.1 vs. 85.5,p = 0.036).Left ventricular mass(LVM)-z-score and LVM index were significantly higher in the PKU group than in the healthy control group(LVM z-score 0.9 vs. 0.5,p = 0.014 and LVM index 38.9 vs. 32.7 g/m2.7,p = 0.001). A moderately statistically significant positive correlation was found between the mean phenylalanine(phe) value and pulse wave velocity(PWV) among the PKU patient groups(R: 0.477,p < 0.001).A moderately statistically significant positive correlation was also found between waist circumference and PWV in the PKU patient group(R:0.541, p < 0.001). CONCLUSIONS: Our study found that close follow-up of phe levels and PWV is more critical than obesity, GI, and GL in the cardiovascular evaluation of classical PKU patients.A large number of multicenter pediatric studies are needed in this area.

Assessment of the oxidative damage and apoptotic pathway related to furan cytotoxicity in cultured mouse Leydig cells.

Research on heat-induced food contamination is being given more attention as a result of the health risks that have been publicly revealed in recent years. Furan is known as a colorless, combustible, heterocyclic aromatic organic molecule and is formed when food products are processed and stored. It has been established that furan, which is inevitably ingested, has a deleterious impact on human health and causes toxicity. Furan is known to have adverse effects on the immune system, neurological system, skin, liver, kidney, and fat tissue. Infertility caused by furan is a result of its damaging effects on several tissues and organs as well as the reproductive system. Although studies on the adverse effects of furan on the male reproductive system have been performed, there is no study revealing apoptosis in Leydig cells at the gene level. In this study, TM3 mouse Leydig cells were exposed to 250- and 2,500-µM concentrations of furan for 24 h. The findings demonstrated that furan decreased cell viability and antioxidant enzyme activity while increasing lipid peroxidation, reactive oxygen species, and apoptotic cell rates. Furan also increased the expression of the important apoptotic genes Casp3 and Trp53 while decreasing the expression of another pro-apoptotic gene, Bcl2, and antioxidant genes Sod1, Gpx1, and Cat. In conclusion, these results imply that furan may cause loss of cell function in mouse Leydig cells responsible for testosterone biosynthesis by impairing the efficiency of the antioxidant system, possibly by inducing cytotoxicity, oxidative stress, and apoptosis.

Inherited Metabolic Diseases from Past to Present: A Bibliometric Analysis (1968-2023).

Bibliometric studies on inherited metabolic diseases (IMDs) do not exist in the literature. Therefore, our research aims to conduct a bibliometric study to determine the current status, trending topics, and missing points of publications on IMDs. Between 1968 and 2023, we conducted a literature search with the keyword "inherited metabolic disease" in the SCOPUS database. We included research articles in medicine written in English and published in the final section. We created our data pool using VOSviewer, SciMAT, and Rstudio software programs for the bibliometric parameters of the articles that met the inclusion criteria. We performed a bibliometric analysis of the data with the R package "bibliometrix" and BibExcel programs. We included 2702 research articles published on IMDs. The top three countries that have written the most articles in this field are the USA (n = 501), the United Kingdom (n = 182), and China (n = 172). The most preferred keywords by the authors were: newborn screening (n = 54), mutation (n = 43), phenylketonuria (n = 42), children (n = 35), genetics (n = 34), and maple syrup urine disease (n = 32). Trending topics were osteoporosis, computed tomography, bone marrow transplantation in the early years of the study, chronic kidney disease, urea cycle disorders, next-generation sequencing, newborn screening, and familial hypercholesterolemia in the final years of the study. This study provides clinicians with a new perspective, showing that molecular and genetic studies of inherited metabolic diseases will play an essential role in diagnosis and treatment in the future.

Furan promotes cytotoxic effects through DNA damage and cell apoptosis in Leydig cells.

Furan is an organic chemical that can cause adverse effects on human health and is formed as a result of the thermal decomposition of many food components during cooking, storage, and processing techniques. Studies have shown that exposure to furan causes nephrotoxicity, hepatotoxicity, immunotoxicity, and reproductive toxicity. According to our current knowledge of the literature, the genotoxic mode of action of furan is highly controversial. The genotoxic effects of furan on the male reproductive system, however, have not been studied. In this study, the TM3 Leydig cell line was treated with 750, 1500, and 3000 µM concentrations of furan for 24 h. Following the completion of the exposure period, the cytotoxicity of furan in TM3 Leydig cells was assessed using a cell viability assay and a spectrophotometric measurement of lactate dehydrogenase (LDH) enzyme levels. The double fluorescence staining method was used to demonstrate furan-induced apoptosis, and DNA damage was shown using the micronucleus, comet, and chromosomal aberration assays. The result indicated that furan administration of Leydig cells resulted in an increase in structural chromosomal aberration, comet, and micronucleus formation, reduced cell viability, increased LDH activity, and a higher incidence of apoptotic cells. These findings revealed that furan induces DNA damage in TM3 Leydig cells, causing genotoxicity and DNA damage-induced cytotoxicity.

The Effect of the Meditation Based Mandala Programme on Distress, Anxiety and Depression in the Caregivers of Cancer Patients in Palliative Care Unit.

Mental health problems were found to be more common than physical health problems in cancer caregivers in palliative care units. This is a quasi-experimental study planned to determine the effect of the meditation based mandala programme on distress, anxiety and depression in caregivers of cancer patients in a palliative care unit. Planned as a single-group pre-test/post-test design, with a total of 11 caregivers. Data were collected with the Caregiver Diagnosis Form, Distress Thermometer, Beck Depression Inventory, and Beck Anxiety Inventory. Caregivers participated in the Meditation Based Mandala Programme once a week, which lasted 2 hours for 5 weeks. The distress, depression and anxiety levels of the patients were measured before the programme started and at the end of the programme. Meditation based mandala programme is effective in reducing the distress, depression and anxiety levels of caregivers of cancer patients in the palliative care unit.

The Relationship Between Depression, Anxiety, and Stress Levels and Eating Behavior in Emergency Service Workers.

Introduction It is seen that shift work causes various biological, psychological, and behavioral problems in individuals. This study aimed to determine the eating attitudes and behaviors of health workers working in shifts in a stressful environment such as the emergency service and to examine the relationship between depression, anxiety, and stress levels and eating behaviors (emotional eating, restrictive eating, and external eating) in terms of sociodemographic and clinical characteristics. Material and Methods Sociodemographic data form; Depression, Anxiety, and Stress Scale (DASS); and Dutch Eating Behavior Questionnaire (DEBQ) were used. The study sample consisted of 92 employees (doctor, nurse, emergency medical technician (EMT), medical secretary, and security, staff) who were actively on duty in the emergency department of Alanya Alaaddin Keykubat University Medical Faculty Training and Research Hospital. Results In our study, when the eating behavior of emergency service workers was evaluated in terms of "emotional, external, and restricted eating" sub-dimensions, depression (p=0.043), anxiety (p=0.017), increased stress levels (p=0.002), being female (p=0.022), nurse-emergency medical technician profession (p=0.001), working in 24-hour shifts (p=0.001), and diet history (p=0.013) were associated with "emotional eating." In addition, an increase in depression levels (p=0.048), being single (p=0.015), working in 24-hour shifts (p=0.005), a decrease in age (p<0.001) with "extrinsic eating," an increase in body mass index (BMI) (p=0.020) and waist circumference (p=0.049), and diet history (p<0.001) were associated with "restricted eating." Conclusions In our study, among the sociodemographic factors, being female, being single, working in 24-hour shifts, diet history, nurse-EMT profession, and undergraduate education level were found to increase the tendency to develop eating behavior problems. An increase in depression levels, being single, working in 24-hour shifts, and a decrease in age were associated with "extrinsic eating." There is a correlation between depression, anxiety, and stress scores and emotional eating scores. Additionally, we found significant correlations between body mass index, waist circumference, diet history, and restricted eating scores. In the approach to eating behavior problems, it is important to determine the individual eating behavior disorder. Due to the increased risk of eating behavior disorder in those who work in long shifts such as 24 hours, it will be possible to organize work programs and increase the quality of service.

Dynamic assessment of the relationship between oxidative stress and apoptotic pathway in embryonic fibroblast cells exposed to glycidamide: possible protective role of hesperidin.

Worldwide research is being conducted to determine the level of acrylamide (ACR) that humans are exposed to from food and environmental sources. Glycidamide (GA) is an important epoxide metabolite of ACR, and its cytotoxicity is stronger than ACR. In this study, it was aimed to elucidate the effects and underlying mechanisms of GA on the induction of apoptosis in embryonic fibroblast cells. The toxicogenomic profile of GA was studied in terms of both apoptotic and oxidative stress. Embryonic fibroblast cells were exposed to GA (1 and 1000 µM) in the presence and absence of hesperidin (Hes) (20 µM) or vitamin C (VitC) (50 µM) for 24 h. Cell viability, cytotoxicity, lipid peroxidation, hydroxyl radicals, hydrogen peroxide, antioxidant enzyme levels and gene expressions, apoptotic, and oxidative stress-related gene expressions were measured in embryonic fibroblast cells. The results showed that GA induced cytotoxicity and diminished the expression levels of apoptotic genes. Furthermore, GA increased the levels of oxidative stress markers and significantly changed the oxidative stress-related gene expression. It has been determined that antioxidant molecules are considerably suppressed in GA-induced toxicity at both gene and enzyme levels. In addition to these results, when VitC, which is known to have strong antioxidant properties in eliminating the toxic effects of GA, is taken as reference, it has been proven that Hes has stronger antioxidant properties compared to VitC. Finally, GA-induced apoptosis in embryonic fibroblast cells is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent oxidative stress and Hes has antioxidant properties with strong effects.

Improving Risk Stratification of Patients With Chest Pain in the Emergency Department.

OBJECTIVE: The HEARTS3 score is used to predict acute coronary syndrome by evaluating the findings of chest pain patients at the end of the second hour. Additionally, the American College of Cardiology (ACC)/American Heart Association (AHA) 2014 non-ST elevation acute coronary syndrome (NSTE-ACS) management guideline suggests assessing cardiac troponin levels at the third and sixth hours as a class 1A recommendation. This study aimed to explore the value of the HEARTS3 score for the evaluation of patients with chest pain and its utility for determining whether a patient is eligible for early discharge from the emergency department. MATERIAL AND METHODS: This study was prospectively conducted between March 1, 2016 to May 31, 2016 at the ED of the Research and Training Hospital in Istanbul. A total of 136 patients were evaluated, and HEARTS3 scores were calculated at the second, third, and sixth hours. Receiver operating characteristic (ROC) curves were used to calculate the specificity, sensitivity, negative predictive value (NPV) and positive predictive value (PPV) of these scores. The primary outcome was the occurrence of major adverse cardiac events (MACEs) within 30 days. RESULTS: In total, 29 patients with MACEs and 107 patients without MACEs were identified within 30 days. Based on the ROC curve, the cutoff value for early discharge was 6. The area under curve (AUC) values were 0.943, 0.963 and 0.976 at the second, third, and sixth hours, respectively. The sensitivity of the second-hour HEARTS3 score was 96.6%, and the NPV was 98.6%. Both the sensitivity and NPV reached 100% at the sixth hour. CONCLUSION: The HEARTS3 score was considered a feasible method for the prediction of MACEs. We concluded that a patient with a HEARTS3 score less than 6 may be discharged without serial troponin and ECG examination.

Expression of ER stress markers (GRP78 and PERK) in experimental nephrotoxicity induced by cisplatin and gentamicin: roles of inflammatory response and oxidative stress.

This study aimed to establish the relationship between two endoplasmic reticulum (ER) stress proteins, glucose-regulated protein 78 (GRP78/BiP) and PKR-like endoplasmic reticulum kinase (PERK), and oxidative stress markers in cisplatin (CIS)-induced and gentamicin (GEN)-induced nephrotoxicity.The study consisted of five groups: control (saline solution only), CIS D2 (2.5 mg/kg for 2 days), CIS D7 (2.5 mg/kg for 7 days), GEN D2 (160 mg/kg for 2 days), and GEN D7 (160 mg/kg for 7 days). All rats were sacrificed 24 h after the last injection for standard clinical chemistry, and ultrastructural and histological evaluation of the kidney.CIS and GEN increased blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as total oxidant status (TOS), while decreasing total antioxidant status (TAS) level in CIS D7 and GEN D7 groups. Histopathological and ultrastructural findings were also consistent with renal tubular damage. In addition, expression of markers of renal inflammation (tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß)) and ER stress markers (GRP78 and PERK) was significantly increased in the kidney tissue of rats treated with CIS and GEN for 7 days.These findings suggest that CIS and GEN administration for 7 days aggravates nephrotoxicity through the enhancement of oxidative stress, inflammation, and ER stress-related markers. As a result, the recommended course of action is to utilize CIS and GEN as an immediate but brief induction therapy, stopping after 3 days and switching to other drugs instead.

Disruption of Leydig cell steroidogenic function by sodium arsenite and/or sodium fluoride.

Arsenite (As) and fluoride (F), both of which are linked to a variety of human ailments, are regularly found in underground drinking water. Numerous studies have shown that As and/or F have negative impacts on testicular function and fertility. For this purpose, mouse Leydig cells, the main cells responsible for the generation and regulation of steroid hormones such as testosterone, were used to reveal the effects of individual and combined exposure of As and F on the steroidogenic pathway in the male reproductive system. Leydig cells were treated with 0.39 µM (50 ppb) As and 0.0476 mM (2 ppm) F alone and in combination for 24 h. The findings revealed that As and/or F exposure induced oxidative stress and apoptosis in Leydig cells and altered antioxidant equilibrium of the cells by reducing superoxide dismutase, catalase, glutathione peroxidase. Additionally, individual and combined administration of As and/or F significantly supressed the expression of both steroidogenic enzymes and the genes encoding these enzymes. In conclusion, this study showed that exposure to As and F at environmentally relevant concentrations dispersed by water decreased testosterone production in Leydig cells, an important cell of the male reproductive system. The deleterious effects of even the lowest concentrations of As and F elements that can reach humans from the environment on the Leydig cell, and therefore on male infertility, emphasize necessity new safe limits for these elements.

Synergistic effects of arsenic and fluoride on oxidative stress and apoptotic pathway in Leydig and Sertoli cells.

Excessive intake of arsenic (As) and fluoride (F), which are present in underground drinking water, have adverse effects on human health, and especially on the male reproductive system. In this regard, it's critical to figure out how As and F affect Leydig and Sertoli cells, which are key cells in the male reproductive system. The goal of this study was to determine the synergistic effects of co-exposure of As and F, via drinking water, on Leydig and Sertoli cells, which are models for the male reproductive system, as well as the mechanisms underlying these effects in terms of oxidative damage and apoptosis. Leydig and Sertoli cells were exposed to concentrations of 7.7 µM (0.57 ppm) As and 0.4 mM (7.24 ppm) F based on the highest daily intake of drinking water for 24 h. The present results revealed that As and/or F treatment reduced cell viability and proliferation in Leydig and Sertoli cells, elevated lactate dehydrogenase, a cytotoxicity marker, and triggered oxidative stress and apoptosis. Furthermore, it has been proven that when As and F are exposed in combination, they have a synergistic effect. In conclusion, by revealing the harmful effects of As and F on Leydig and Sertoli cells, and thus on male infertility, it is possible to reduce As and F exposure to prevent infertility after exposure to these molecules not only separately but also together. It will be considered to determine new action and action plans to reduce As and F exposure.

Antilipidemic ezetimibe induces regression of endometriotic explants in a rat model of endometriosis with its anti-inflammatory and anti-angiogenic effects.

To assess the potential therapeutic role of antilipidemic ezetimibe on endometriosis in an experimental rat model. A standard experimental endometriosis model was created with 18 Whistar-Albino rats, and after 1 month, the sizes of the endometriotic explants were measured. The rats were randomized as study and control groups. A total of 1 mg/kg/day ezetimibe and 1 ml/kg/day saline were administered orally to the study and control groups respectively for 28 days. At the end of 28 days, the explants were measured again, excised, and sent for histopathologic assessment for expression of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) and number of mast cells. At the end of the study period, the size of the endometriotic explants decreased significantly in the study group; but not in the control group (from 145.3 ± 120.5 to 89.8 ± 60.1 vs 174.72 ± 88.3 to 87.65 ± 27.1 cm3 respectively); however, the amount of post- and pretreatment differences in explant sizes was similar in the groups. The median TNF-α and VEGF levels were significantly lower in the ezetimibe group when compared to the control group (4 [3-4] vs 2 [1-3], p 0.029; 4 [3-4] vs 2 [2-3], p 0.002; respectively). And numbers of mast cells in all uterine layers were also lower in the ezetimibe group. Ezetimibe decreased the size of the endometriotic explants with its anti-inflammatory and anti-angiogenic properties. This agent alone or with combination of other agents may have a potential role in the treatment of endometriosis.

False recognitions in the DRM paradigm: the role of stress and warning.

For the last decades, the factors increasing or decreasing the frequency of false memories have been of great interest. Some research also examined the effect of stress and warning on the true and false recognitions; however, so far most of the studies have yielded contradictory results or seems inadequate to understand the effect of these factors on false memory phenomenon. The purpose of this study is to examine the joint effects of stress and warning on the frequency of false and true memories elicited by the list-learning paradigm. The word lists derived from the Deese-Roediger-McDermott (DRM) paradigm were used in order to measure false and true recognition rates. Participants (N = 126) were exposed to either the Trier Social Stress Test (a stress condition) or a filler task at the beginning of the experiment (no-stress condition). Then, they were either subjected to a warning about false memories before DRM (pre-warning condition), subjected to a warning about false memories after DRM (post-warning condition), or given no warning at all (no-warning condition). Results showed that stress had a statistically significant effect on true recognition but not on false recognition. Furthermore, warning given after the DRM lists had a decreasing effect on the frequency of false memories. No significant interaction effect between stress and warning was found. Although our hypotheses were not confirmed, this study can contribute to the existing body of research by providing evidence that stress and warning have differential effects on both true and false memories derived from the DRM paradigm.

Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

Evaluation of renal transplantation recipients those who do not use steroid with panel reactive antibody and donor specific antibody / Evaluación de receptores de trasplante renal que no usan esteroides con panel de anticuerpos reactivos y anticuerpos específicos del donante

ABSTRACT Background: Steroids are the mainstream drugs of immu- nosuppressive regimen in renal transplantation. They are successfully used on induction, maintenance and rejection treatment. Due to complications caused by steroids, treatments are switched to immunosuppressive agents. Graft dysfunction risk caused by reduced total immunosuppression disturbs clinicians very often. We documented the differences among patients by means of clinical presentation and PRA/DSA levels between patients who are using steroids and patients that were prescribed for steroid-free regimen. Methods: 82 individuals who did not use steroid and 52 patients on steroid treatment were included with similar rates of age, sex, primary renal disease, dialysis type, posttransplant follow-up duration and donor type. Pre and posttransplant PRA, DSA levels, posttransplant and current graft function and comorbidities were evaluated. Results: Individuals who do not use steroids were found to have a lower posttransplant creatinine level and glomerular filtration rate (GFR) compared to steroid users. Posttransplant and current spot urinary protein/creatinine rates were also lower in the steroid-free group. However DM, BKVN and induction therapy rates were higher in the steroid-free group. PRA and DSA levels were similar in both groups. On the other hand, posttransplant PRA-I levels were significantly higher in those with less steroid use time. Conclusions: Although steroid free regimens usually worry the clinicians, they can be preferred in patients with low immunological risk for rejection to avoid its side effects such as uncontrolled diabetes, obesity, musculoskeletal problems and cataracts.

RESUMEN Antecedentes: Los esteroides son los principales fármacos del régimen inmunosupresor en el trasplante renal. Se utilizan con éxito en tratamientos de inducción, mantenimiento y rechazo. Debido a las complicaciones causadas por los esteroides, los tratamientos se cambian a agentes inmunosupresores. El riesgo de disfunción del injerto causado por la reducción de la inmunosupresión total perturba a los médicos con mucha frecuencia. Documentamos la diferencia entre los pacientes por medio de la presentación clínica y los niveles de PRA/DSA en aquellos que utilizan esteroides y a los que se les prescribió un regimen sin esteroides. Material y métodos: Se incluyeron 82 individuos que no usaban esteroides y 52 pacientes en tratamiento con esteroides con tasas similares de edad, sexo, enfermedad renal primaria, tipo de diálisis, duración del seguimiento postrasplante y tipo de donante. Se evaluaron la ARP pre y postrasplante, los niveles de DSA, la función y comorbilidades postrasplante y actual del injerto. Resultados: Se encontró que las personas que no usan esteroides tienen un nivel de creatinina postrasplante y una tasa de filtración glomerular (TFG) más bajas en comparación con los usuarios de esteroides. Las tasas de proteína/creatinina urinarias postrasplante y puntuales actuales también fueron más bajas en el grupo sin esteroides. Sin embargo, las tasas de DM, BKVN y terapia de inducción fueron más altas en el grupo sin esteroides. Los niveles de PRA y DSA fueron similares en ambos grupos. Por otro lado, los niveles de PRA-I postrasplante fueron significativamente más altos en aquellos con menos tiempo de uso de esteroides. Conclusiones: Aunque los regimenes libres de esteroides suelen preocupar a los clínicos, pueden ser preferidos en pacientes con bajo riesgo inmunológico de rechazo para evitar sus efectos secundarios, como diabetes no controlada, obesidad, problemas musculoesqueléticos y cataratas.

Immunological Results of Long-Term Use of Mammalian Target of Rapamycin (mTOR) Inhibitors and Its Effects on Renal Graft Functions.

BACKGROUND Calcineurin inhibitor drugs (CNI), which are the basis of immunosuppression in kidney transplantation, contribute to renal graft loss, with increased morbidity and mortality due to their potentially harmful effects on the renal graft, cardiovascular system, and tumor pathology. For this reason, the mammalian target of rapamycin inhibitors (mTORi) such as sirolimus (SRL) and everolimus (EVE) has been preferred more frequently, as they are associated with fewer complications and longer graft function. MATERIAL AND METHODS We enrolled 89 adult renal transplant patients (37 patients on mTORi and 52 on CNI) who had similar age, sex, primary renal disease, dialysis type, post-transplant follow-up period, and donor type. We analyzed and compared the data between patients using mTORi for longer than 5 years and those using CNI regarding pre- and post-transplant panel reactive antibody (PRA), and donor-specific antibody (DSA), as well as post-transplantation and current graft functions. RESULTS Although those using mTORi for more than 5 years had significantly higher mismatch rates (P=0.024) than those using CNI, there was no significant change in PRA and DSA levels. Transplant time was longer in mTORi users (P=0.025). The switch time to mTORi in patients ranged from 0 to 19 years, but the average was 4 years. As expected, actual spot urine protein/creatinine was significantly higher in those using mTORi (P=0.009). Diabetes mellitus (DM) and BK virus nephropathy (BKVN) rates were significantly higher due to switching the regimen from CNI to mTORi. CONCLUSIONS Long-term use of mTORi does not appear to be an immunological problem.