Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing.

The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.

Exploring free amino acid profiles in CCHF patients: Implications for disease progression.

This study investigated the intricate interplay between Crimean-Congo hemorrhagic fever virus (CCHFV) infection and alterations in amino acid metabolism. Our primary aim is to elucidate the impact of Crimean-Congo hemorrhagic fever (CCHF) on specific amino acid concentrations and identify potential metabolic markers associated with viral infection. One hundred ninety individuals participated in this study, comprising 115 CCHF patients, 30 CCHF negative patients, and 45 healthy controls. Liquid chromatography-tandem mass spectrometry techniques were employed to quantify amino acid concentrations. The amino acid metabolic profiles in CCHF patients exhibit substantial distinctions from those in the control group. Patients highlight distinct metabolic reprogramming, notably characterized by arginine, histidine, taurine, glutamic acid, and glutamine metabolism shifts. These changes have been associated with the underlying molecular mechanisms of the disease. Exploring novel therapeutic and diagnostic strategies addressing specific amino acids may offer potential means to mitigate the severity of the disease.

Transcriptome-wide analysis uncovers regulatory elements of the antennal transcriptome repertoire of bumblebee at different life stages.

Bumblebees are crucial pollinators, providing essential ecosystem services and global food production. The success of pollination services relies on the interaction between sensory organs and the environment. The antenna functions as a versatile multi-sensory organ, pivotal in mediating chemosensory/olfactory information, and governs adaptive responses to environmental changes. Despite an increasing number of RNA-sequencing studies on insect antenna, comprehensive antennal transcriptome studies at the different life stages were not elucidated systematically. Here, we quantified the expression profile and dynamics of coding/microRNA genes of larval head and antennal tissues from early- and late-stage pupa to the adult of Bombus terrestris as suitable model organism among pollinators. We further performed Pearson correlation analyses on the gene expression profiles of the antennal transcriptome from larval head tissue to adult stages, exploring both positive and negative expression trends. The positively correlated coding genes were primarily enriched in sensory perception of chemical stimuli, ion transport, transmembrane transport processes and olfactory receptor activity. Negatively correlated genes were mainly enriched in organic substance biosynthesis and regulatory mechanisms underlying larval body patterning and the formation of juvenile antennal structures. As post-transcriptional regulators, miR-1000-5p, miR-13b-3p, miR-263-5p and miR-252-5p showed positive correlations, whereas miR-315-5p, miR-92b-3p, miR-137-3p, miR-11-3p and miR-10-3p exhibited negative correlations in antennal tissue. Notably, based on the inverse expression relationship, positively and negatively correlated microRNA (miRNA)-mRNA target pairs revealed that differentially expressed miRNAs predictively targeted genes involved in antennal development, shaping antennal structures and regulating antenna-specific functions. Our data serve as a foundation for understanding stage-specific antennal transcriptomes and large-scale comparative analysis of transcriptomes in different insects.

Comprehensive analysis of circulating viral DNA in maternal plasma at population-scale using low-pass whole-genome sequencing.

As the most readily adopted molecular screening test, low-pass WGS of maternal plasma cell-free DNA for aneuploidy detection generates a vast amount of genomic data. This large-scale method also allows for high-throughput virome screening. NIPT sequencing data, yielding 6.57 terabases of data from 187.8 billion reads, from 12,951 pregnant Turkish women was used to investigate the prevalence and abundance of viral DNA in plasma. Among the 22 virus sequences identified in 12% of participants were human papillomavirus, herpesvirus, betaherpesvirus and anellovirus. We observed a unique pattern of circulating viral DNA with a high prevalence of papillomaviruses. The prevalence of herpesviruses/anellovirus was similar among Turkish, European and Dutch populations. Hepatitis B prevalence was remarkably low in Dutch, European and Turkish populations, but higher in China. WGS data revealed that herpesvirus/anelloviruses are naturally found in European populations. This represents the first comprehensive research on the plasma virome of pregnant Turkish women.

The Beneficial Clinical Effects of Teriflunomide in Experimental Autoimmune Myasthenia Gravis and the Investigation of the Possible Immunological Mechanisms.

Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disease characterized by skeletal muscle weakness exacerbated with exercise. There is a need for novel drugs effective in refractory MG. We aimed to test the potential of teriflunomide, an immunomodulatory drug currently used in rheumatoid arthritis and multiple sclerosis treatment, in a murine experimental autoimmune myasthenia gravis (EAMG) model. EAMG was induced by immunizations with recombinant acetylcholine receptor (AChR). Teriflunomide treatment (10 mg/kg/day, intraperitoneal) was initiated to one group of mice (n = 21) following the third immunization and continued for 5 weeks. The disease control group (n = 19) did not receive medication. Naïve mice (n = 10) received only mock immunization. In addition to the clinical scorings, the numbers of B cells and T cells, and cytokine profiles of T cells were examined by flow cytometry. Anti-AChR-specific antibodies in the peripheral blood serum were quantified by ELISA. Teriflunomide significantly reduced clinical disease scores and the absolute numbers of CD4+ T cells and some of their cytokine-producing subgroups (IFN-γ, IL 2, IL22, IL-17A, GM-CSF) in the spleen and the lymph nodes. The thymic CD4+ T cells were also significantly reduced. Teriflunomide mostly spared CD8+ T cells' numbers and cytokine production, while reducing CD138+CD19+lambda+ plasma B cells' absolute numbers and CD138 mean fluorescent intensities, probably decreasing the number of IgG secreting more mature plasma cells. It also led to some selective changes in the measurements of anti-AChR-specific antibodies in the serum. Our results showed that teriflunomide may be beneficial in the treatment of MG in humans.

Safety and efficacy of mesenchymal stromal cell therapy for multi-drug-resistant acute and late-acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.

Graft versus host disease (GvHD) remains a significant risk for mortality and morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). A growing literature supports successful applications of mesenchymal stromal cells (MSCs) for the treatment of steroid-refractory acute GvHD (aGvHD). However, there is limited knowledge about the effects of MSC treatment on late-acute GvHD (late aGvHD). In this article, we present our multicenter study on the safety and efficacy of MSC therapy for patients with steroid-refractory late aGvHD in comparison to those with aGvHD. The outcome measures include non-relapse mortality (NRM) and survival probability over a 2-year follow-up. The study includes a total of 76 patients with grades III-IV aGvHD (n = 46) or late aGvHD (n = 30), who had been treated with at least two lines of steroid-containing immunosuppressive therapy. Patients received weekly adipose or umbilical cord-derived MSC infusions at a dose of median 1.55 (ranging from 0.84 to 2.56) × 106/kg in the aGvHD group, and 1.64 (ranging from 0.85 to 2.58) × 106/kg in the late aGvHD group. This was an add-on treatment to ongoing conventional pharmaceutical management. In the aGvHD group, 23 patients received one or two infusions, 20 patients had 3-4, and three had ≥ 5. Likewise, in the late aGvHD group, 20 patients received one or two infusions, nine patients had 3-4, and one had ≥ 5. MSC was safe without acute or late adverse effects in 76 patients receiving over 190 infusions. In aGvHD group, 10.9% of the patients had a complete response (CR), 23.9% had a partial response (PR), and 65.2% had no response (NR). On the other hand, in the late aGvHD group, 23.3% of the patients had CR, 36.7% had PR, and the remaining 40% had NR. These findings were statistically significant (p = 0.031). Also, at the 2-year follow-up, the cumulative incidence of NRM was significantly lower in patients with late aGvHD than in patients with aGvHD at 40% (95% CI, 25-62%) versus 71% (95% CI, 59-86%), respectively (p = 0.032). In addition, the probability of survival at 2 years was significantly higher in patients with late aGvHD than in the aGvHD group at 59% (95% CI, 37-74%) versus 28% (95% CI, 13-40%), respectively (p = 0.002). To our knowledge, our study is the first to compare the safety and efficacy of MSC infusion(s) for the treatment of steroid-resistant late aGVHD and aGVHD. There were no infusion-related adverse effects in either group. The response rate to MSC therapy was significantly higher in the late aGvHD group than in the aGvHD group. In addition, at the 2-year follow-up, the survival and NRM rates were more favorable in patients with late aGVHD than in those with aGVHD. Thus, the results are encouraging and warrant further studies to optimize MSC-based treatment for late aGVHD.

Relationship Between Temporomandibular Ankylosis And Maximum Mouth Opening In Children.

BACKGROUND: Pediatric dentists should have information regarding whether mouth opening is limited. In clinical practice, these professionals should collect and record oral area measurements at the pediatric patient's first medical examination. OBJECTIVES: The study's aim developed the standard mouth opening measurement in children by using ordinary least squares regression to develop a clinical prediction model in children with Temporomandibular Joint Ankylosis before preoperative surgery. METHODS: All participants completed their age, gender, and calculated height, weight, body mass index, and birth weight. Pediatric dentist performed all mouth-opening measurements. The oral-maxillofacial surgeon marked subnasal and pogonion points for the lower facial length of soft tissue. It was measured using the distance between the subnasal and pogonion with a digital vernier caliper. The widths of the three fingers (index, middle, and ring fingers) and four fingers (index, middle, ring, and little fingers) were also measured using a digital vernier caliper. RESULTS: Maximum mouth opening showed that three-finger width (R2 = 0.566, F = 185.479) and four-finger width (R2 = 0.462, F = 122.209) had a significant influence on the Maximum mouth opening (MMO) (p < 0.001). CONCLUSION: Pediatric dentists should collaborate with the treating maxillofacial surgeon to manage long-term treatment needs for individuals with Temporomandibular Joint Ankylosis.

The Characterization of Sex Differences in Hypoglycemia-Induced Activation of HPA Axis on the Transcriptomic Level.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis using an insulin tolerance test (ITT) is a medical diagnostic procedure that is frequently used in humans to assess the HPA and growth-hormone (GH) axes. Whether sex differences exist in the response to ITT stress is unknown. Thus, investigations into the analysis of transcripts during activation of the HPA axis in response to hypoglycemia have revealed the underlying influences of sex in signaling pathways that stimulate the HPA axis. We assessed four time points of ITT application in Balb/c mice. After insulin injection, expression levels of 192 microRNAs and 41 mRNAs associated with the HPA, GH and hypothalamic-pituitary-gonadal (HPG) axes were determined by real-time RT-PCR in the hypothalamus, pituitary and adrenal tissues, as well as blood samples (Raw data accession: https://drive.google.com/drive/folders/10qI00NAtjxOepcNKxSJnQbJeBFa6zgHK?usp=sharing ). Although the ITT is commonly used as a gold standard for evaluating the HPA axis, we found completely different responses between males and females with respect to activation of the HPA axis. While activation of several transcripts in the hypothalamus and pituitary was observed after performing the ITT in males within 10 min, females responded via the pituitary and adrenal immediately and durably over 40 min. Additionally, we found that microRNA alterations precede mRNA responses in the HPA axis. Furthermore, robust changes in the levels of several transcripts including Avpr1b and Avpr2 observed at all time points strongly suggest that transcriptional control of these genes occurs mostly via differential signaling in pituitary and blood between males and females. Male and female HPA axis responses to ITT involve a number of sophisticated regulatory signaling pathways of miRNAs and mRNAs. Our results highlight the first robust markers in several layers of HPA, HPG and GH axis involved in ITT/hypoglycemia stress-induced dynamics.

Survival of biological therapeutics in psoriasis: retrospective analysis of 3-years data in a Turkish registry, PSORTAKSIS.

BACKGROUND: TPSORTAKSIS is a psoriasis registry, which is used for follow-up of patients in Kayseri City Education and Research Hospital, Dermatology Clinic since 2016 in Turkey. PSORTAKSIS includes demographic data, follow-up clinical findings, laboratory output, and treatment information of patients. Here, drug survivals of biologic therapeutics (BT) according to three-year data of PSORTAKSIS will be presented. METHODS: Drug survival of BT in PSORTAKSIS was analyzed from 2016 to March 2019. RESULTS: 158 patients (111 of them BT-naive) with psoriasis under BT were enrolled in the current study. Drug survival analysis of patients with ongoing BT (158 treatment periods) revealed mean survival time as 15.49 months for ustekinumab, 15.37 months for adalimumab, 14.00 months for etanercept, 5 months for infliximab, and 4.59 months for secukinumab. The differences between drug survivals of BT were statistically significant (log-rank test, χ2 = 79.915, p < 0.0001).

Different threshold levels of circulating total and free 25-hydroxyvitamin D for the diagnosis of vitamin D deficiency in obese adolescents.

The total serum 25-hydroxyvitamin D [25(OH)DT] level is lower in obese individuals than in their nonobese peers, despite similar bone turnover markers and bone mineral density. This study aimed to investigate whether the threshold level of 25(OH)D for the diagnosis of vitamin D deficiency (VDD) in obese adolescents was lower than that in controls and to compare 25(OH)DT, free [25(OH)DF] and bioavailable [25(OH)DB] vitamin D with VDBP levels in obese individuals and their controls. A total of 173 adolescents (90 obese individuals and 83 controls) aged 12-18 years were included in the study. The metabolic and anthropometric parameters of the participants were recorded, the 25(OH)DT, 25(OH)DF, and VDBP levels were measured, and the 25(OH)DB levels were calculated. The cutoff values for VDD were estimated according to the level of 25(OH)D below which parathyroid hormone begins to rise. The obese subjects had lower 25(OH)DT (12.1 ± 5.8 vs. 16.4 ± 9.3 ng/mL, p < 0.001), 25(OH)DF (12.6 ± 4.2 vs. 16.7 ± 7.6 pg/mL, p < 0.001), 25(OH)DB [4.8 (2.3) vs. 6.1 (5.2) ng/mL, p = 0.012], and VDBP [112.2 (51.3) vs. 121.9 (95.5) µg/mL, p < 0.001] levels than the controls. The cutoff values for 25(OH)DT and 25(OH)DF levels for VDD were lower in the obese group than in the control group (9.4 vs. 14.1 ng/mL; 12.2 vs. 16.8 pg/mL, respectively).Conclusion: The vitamin D cutoff values for the diagnosis of VDD were different in the obese and control groups. Using the same cutoff value for VDD may cause overtreatment in obese adolescents. What is Known: • Vitamin D deficiency is more prevalent in obese children than nonobese controls, despite the same bone turnover markers and bone mineral density • The cutoff value of vitamin D level for the diagnosis of VDD is based on the PTH elevation What is New: • In obese adolescents, total and free vitamin D cutoff value for the diagnosis of VDD was lower than nonobese peers • Using the same cutoff value for vitamin D deficiency in both obese and nonobese adolescents may cause overtreatment.

Hypoxia-inducible factors in arteriovenous fistula maturation: A prospective cohort study.

BACKGROUND: Neointimal hyperplasia is the main cause of arteriovenous fistula (AVF) failure. Hypoxia-inducible factors (HIFs) factors are associated with neointimal hyperplasia. Thus, we investigated the association between HIF-2 alpha (HIF-2α) and AVF maturation in end-stage kidney disease (ESKD) patients. METHODS: This prospective cohort study was conducted in 21 voluntary healthy subjects and 50 patients with ESKD who were eligible for AVF creation. Inclusion criteria were being ESKD patients without a history of AVF surgery and dialysis. Eight patients excluded from the study due to having unavailable veins six patients were excluded due to acute thrombosis after surgery. One patient lost to follow-up. A total of 35 patients were included in final analysis. The blood samples were collected a day before the AVF surgery for biochemical parameters and HIF-2α measurement. HIF-2α levels were measured by the ELISA method. RESULTS: Compared with healthy subjects, ESKD patients had a significantly higher level of HIF-2α. [1.3 (1.0-1.9) vs 2.2 (1.6-3.0)] (P = .002). Patients were divided into two groups after the evaluation of AVF maturation, as the mature group (n = 19) and the failure group (n = 16). Serum HIF-2α level was 1.7 (1.1-1.8) in the mature group; however, it was 3.1 (2.8-3.3 in failure group (P < .001). Multiple logistic regression analyses showed that HIF-2α independently predicted AVF maturation. The ROC curve analysis showed that HIF-2α > 2.65 predicted AVF maturation failure with the 87% sensitivity and 94% specificity [AUC:0.947, 95% CI (0.815-0.994), P < .001]. CONCLUSIONS: HIF-2-α levels were higher in ESKD patients than healthy subjects. HIF-2-α could be a marker of AVF maturation failure.

Autosomal dominant polycystic kidney disease: new role for ultrasound.

OBJECTIVES: To evaluate the accuracy of US in calculating renal volumes and renal resistive index (RRI) that was obtained using a new method in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: In this prospective study, US and MRI were performed in 57 patients with ADPKD (31 female and 26 male; age range, 19-79 years) between August 2017 and May 2018. The volumes determined using US and MRI were compared. The ellipsoid formula was re-evaluated using different multipliers. RRI was obtained 1.5-2 cm distal to the outlet of main renal arteries. The relationship between mean RRI, renal function tests, and kidney volumes and difference between mean RRI of ADPKD patients with and without renal failure were investigated using a two-sided independent samples t test and Pearson correlation test. Interobserver agreements for volume assessments and RRI measurements were determined. RESULTS: By changing the ellipsoid formula, a very good agreement was found (ICC 0.970 for the right kidney and ICC 0.973 for the left kidney). The mean RRI in the right renal artery was 0.61 ± 0.07 and in the left renal artery 0.63 ± 0.06. The mean RRI of ADPKD patients with renal failure was significantly higher than that of patients without renal failure (p = 0.005). There was a significant correlation between mean RRI and renal function tests. CONCLUSION: The accuracy of the US in calculating renal volumes increases by adapting the ellipsoid formula. RRI may be used for the management of ADPKD independently of volumes. KEY POINTS: •The accuracy of ultrasonography for renal volume measurement increases by changing the classical ellipsoid formula. •Renal resistive index measured by color Doppler ultrasonography is helpful for the management of autosomal dominant polycystic kidney disease. •The role of Doppler US in autosomal dominant polycystic kidney disease should increase as a result of our findings.

Multiple urinary tract infections are associated with genotype and phenotype in adult polycystic kidney disease.

BACKGROUND: Urinary tract infections (UTI) are one of the important clinical presentations in patients with autosomal dominant polycystic kidney disease (ADPKD). The association between UTI among genotypic and phonotypic properties of ADPKD patients is still obscure. Thus, we investigated the relationship between UTI and polycystin gene mutation with total kidney volume. METHODS: Forty patients with ADPKD patients with a history of more than two UTI and age-gender-matched 40 ADPKD patients without UTI history enrolled in the study. Ambulatory blood pressure monitoring was performed in all participants. Magnetic resonance imaging (MRI) was performed with a 1.5-T system, and total kidney volumes were calculated using mid-slice technique. To determine PKD1 and PKD2 genotype, we performed molecular and genetic tests involving the following steps: DNA isolation, next-generation sequencing (NGS) and data analysis. RESULTS: ADPKD patients with UTI had lower eGFR values than those without UTI [64.9 (32.2-100.8) vs 89.5 (59.0-110.0) (p = 0.041)]. In addition, patients with UTI had significantly increased height-adjusted total kidney volume than patients without UTI [950 (290-1350) vs 345 (243-780.0) (p = 0.005)]. Multiple logistic regression analysis showed that the PKD1-truncating mutation and hTKV independently predicted UTI. The sensitivity and specificity of hTKV were 65% and 77% (cutoff > 727 cm3) with an area of under the ROC curve of 0.70 (95% CI 0.56-0.85, p = 005). CONCLUSIONS: ADPKD patients with larger kidneys and PKD1 mutation are susceptible to increased risk of multiple UTI. Additionally, renal function decreased in ADPKD patients with multiple UTI history.

The relationship between hematological parameters and prognosis of children with acute ischemic stroke.

BACKGROUND: Stroke is rarely seen in children, but it is a major cause of morbidity and mortality. Therefore, there is a need for inexpensive and noninvasive diagnostic methods for estimating the prognosis. Although the prognostic importance of hematological parameters in acute ischemic stroke were reported in adult studies, there is a lack in pediatric ages. The aim of the study is to investigate the relationship between hematological parameters and prognosis of acute ischemic stroke in children. METHODS: Retrospectively scanned in the study were 106 pediatric patients with acute ischemic stroke who managed at the Medical Faculty of Erciyes University, Kayseri, between the years of 2000 and 2014. White blood count (WBC); neutrophil, lymphocyte, and platelet count; mean platelet volume (MPV); platelet distribution width (PDW); neutrophil count/lymphocyte count (N/L) ratio values obtained from the measurements and initial symptoms; demographical features; risk factors; neurological examination; and clinical follow-up were recorded. Their hematological parameters were compared with those of 106 age and sex-matched healthy individuals. RESULTS: MPV and PDW values were found similar in patient and control groups, and the platelet count was found significantly low in the control group (p = 0,028). WBC, neutrophil count, and N/L ratio were found considerably high in the patient group (p < 0.001). Lymphocyte count, however, was found significantly low in the control group (p < 0.001). No statistically significant difference was detected in WBC, neutrophil count, lymphocyte count, platelet count, N/L ratio, and MPV and PDW values between the group with sequelae and the one without sequelae. In addition, it was determined that WBC, neutrophil count, lymphocyte count, platelet count, N/L ratio, and MPV and PDW values in the univariate Cox-regression analysis of the patient group had no effect on survival and disease-free survival. When receiver operating characteristic curve was applied, it was observed that the area below WBC, N/L ratio curve was important in the patient group in terms of predicting acute ischemic stroke. CONCLUSION: The values of WBC, neutrophil count, and N/L ratio differ significantly from those of the control group. The WBC and N/L ratio may help for an earlier diagnosis in children with acute ischemic stroke. WBC, thrombocyte count, MPV, PDW, and N/L ratio do not constitute a risk in overall survival, disease-free survival, and sequelae development.

The association of profilin-1 levels with survival in chronic kidney disease.

BACKGROUND: Profilin-1 is a ubiquitous, actin-binding protein that plays an important role in the regulation of actin polymerization and cytoskeleton remodelling and contributes to vascular dysfunction. We conducted this study to investigate the association of serum profilin-1 levels with fatal and nonfatal CVE in a cohort of patients with stage 1-5 CKD. MATERIALS AND METHODS: Serum concentrations of profilin-1 levels were determined by enzyme-linked immunosorbent assay. Endothelium-dependent vasodilatation (flow-mediated dilatation [FMD]) and endothelium-independent vasodilatation (nitroglycerine-mediated dilatation [NMD]) of the brachial artery were assessed noninvasively, using high-resolution ultrasound. RESULTS: Both fatal and nonfatal CVE were significantly higher in patients with high profilin-1 levels. Kaplan-Meier survival curves showed that patients with profilin-1 below the median value (114 pg/mL) had higher cumulative survival compared with patients who had profilin-1 levels above the median value (log-rank test, P < .001). CONCLUSIONS: This is the first study that demonstrates the serum profilin-1 is independently associated with endothelial dysfunction, cardiovascular events and survival in patients with CKD.

Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder with unclear disease mechanism. Currently, overt hypertension and increased renal volume are the best predictors of renal function. In this study, we assessed the usefulness of selected circulating microRNAs (miRs) to predict disease progress in a cohort with ADPKD. METHODS: Eighty ADPKD patients (44.6 ± 12.7 years, 40% female, 65% hypertensive) and 50 healthy subjects (HS; 45.4 ± 12.7, 44% female) were enrolled in the study. Serum levels of 384 miRs were determined by Biomark Real Time PCR. Groups were compared using the limma method with multiple-testing correction as proposed by Smyth (corrected p < 0.01 considered significant). RESULTS: Comparing ADPKD to HS, we found significant differences in blood levels of 18 miRs (3 more and 15 less abundant). Of these, miR-3907, miR-92a-3p, miR-25-3p and miR-21-5p all rose while miR-1587 and miR-3911 decreased as renal function declined in both cross-sectional and longitudinal analysis. Using ROC analysis, an increased baseline miR-3907 in the circulation predicted a > 10% loss of GFR over the following 12 months (cut-off >2.2 AU, sensitivity 83%, specificity 78%, area 0.872 [95% CI: 0.790-0.953, p < 0.001]). Adjusting for age and starting CKD stage using multiple binary logistic regression analysis did not abrogate the predictive value. CONCLUSION: Increased copy numbers of miR-3907 in the circulation may predict ADPKD progression and suggest pathophysiological pathways worthy of further study.

Evaluation of the efficacy and safety of original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) in CD34(+) peripheral hematopoietic stem cell mobilization procedures for allogeneic hematopoietic stem cell transplant donors.

OBJECTIVES AND AIM: In this study, we aimed to compare the potency of different G-CSF agents including original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34(+) cell mobilization in patients that underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). PATIENTS AND METHODS: The data of 243 donors for alloHSCT recipients diagnosed with mostly acute leukemia and myelodsyplastic syndromes (MDS) were analyzed, retrospectively. Data for stem cell mobilization have been recorded from patients' files. Donors who received Filgrastim (Neupogen®, Group I), biosimilar Filgrastim (Leucostim®, Group II) and Lenograstim (Granocyte®, Group III) were analyzed for total CD34(+) cell count at the end of mobilization procedures. RESULTS: A total of 243 donors and patients for alloHSCT were analyzed retrospectively. The diagnosis of the patients were; acute myeloid leukemia (AML) (110 patients, 45.2%), acute lymphoid leukemia (ALL) (61 patients, 25.1%), aplastic anemia (AA) (38 patients, 15.6%), lymphomas (14 patients, 5.7%) and others (20 patients, 8.4%). The median number of total collected PB CD34(+) cells (×10(6)/kg) was 7.12 (min-max: 5.38-7.90) in the Neupogen® group, 7.27 (min-max: 6.79-7.55) in the Leucostim® group and 7.15 (min-max: 5.34-7.58) in the Granocyte® group. There was no statistically significant difference among groups in terms of total collected PB CD34(+) cells (p = 0.919). The median doses of G-CSF agents (µg/kg/day) in PBSC collection in Neupogen® group was; 11.00 (10.00-12.00) in Leucostim® group10.35 (min-max: 10.00-11.10) and in Granocyte® group11.00 (min-max: 10.00-11.00). There was no statistical significance among groups (p = 0.215). CONCLUSION: Biosimilar filgrastim (Leucostim®) was found comparable to original Filgrastim (Neupogen®) and Lenograstim (Granocyte®) for PBSC mobilization in donors of the patients that underwent alloHSCT.

The roles of CC2D1A and HTR1A gene expressions in autism spectrum disorders.

Classical autism belongs to a group of heterogeneous disorders known as autism spectrum disorders (ASD). Autism is defined as a neurodevelopmental disorder, characterized by repetitive stereotypic behaviors or restricted interests, social withdrawal, and communication deficits. Numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism but the etiology of this disorder is unknown in many cases. CC2D1A gene has been linked to mental retardation (MR) in a family with a large deletion before. Intellectual disability (ID) is a common feature of autistic cases. Therefore we aimed to investigate the expressions of CC2D1A and HTR1A genes with the diagnosis of autism in Turkey. Forty-four autistic patients (35 boys, 9 girls) and 27 controls were enrolled and obtained whole blood samples to isolate RNA samples from each participant. CC2D1A and HTR1A gene expressions were assessed by quantitative Real-Time PCR (qRT-PCR) in Genome and Stem Cell Center, Erciyes University. Both expressions of CC2D1A and HTR1A genes studied on ASD cases and controls were significantly different (p < 0.001). The expression of HTR1A was undetectable in the ASD samples. Comparison of ID and CC2D1A gene expression was also found statistically significant (p = 0.028). CC2D1A gene expression may be used as a candidate gene for ASD cases with ID. Further studies are needed to investigate the potential roles of these CC2D1A and HTR1A genes in their related pathways in ASD.

The assessment of anterior and posterior ocular structures in hyperopic anisometropic amblyopia.

BACKGROUND: The aim of this study was to examine the relationship or differences in ocular structures of amblyopic eyes compared to fellow eyes in children and young adults with hyperopic anisometropic amblyopia. MATERIAL/METHODS: Hyperopic participants with anisometropic amblyopia, defined as the presence of best-corrected visual acuity differences of at least 2 Snellen lines and 1.5 diopters between amblyopic and fellow eyes, were studied. Using the IOL Master, Pentacam Scheimpflug imaging and Spectralis optical coherence tomography, the axial length, corneal curvature, and anterior chamber depth (ACD), as well as the thickness of the cornea, peripapillary retinal nerve fiber layer (RNFL), and macula, were compared between children and young adults and between their amblyopic and fellow eyes. RESULTS: In 53 participants with hyperopic anisometropic amblyopia, there were significant differences in the anterior corneal curvature, ACD and axial length between the amblyopic and fellow eyes of all the patients. The mean central macular thickness in the amblyopic eyes was significantly thicker (P=.001) in the group aged 5 to 12 years; however, this was not the case in the group aged 13 to 42 years. There was no significant difference in average RNFL thickness in either group. CONCLUSIONS: We found significantly greater mean central macular thickness in anisometropic amblyopic eyes among participants aged 5 to 12 years, but not among those who were older. Similarly, the interocular differences in axial length parameters seemed to be related to the central macular thickness differences between the amblyopic and fellow eyes in the younger group.

Assessment of Macular Peripapillary Nerve Fiber Layer and Choroidal Thickness Changes in Pregnant Women with Gestational Diabetes Mellitus, Healthy Pregnant Women, and Healthy Non-Pregnant Women.

BACKGROUND: Gestational diabetes mellitus (GDM) is a risk factor for the development of type II diabetes and it causes maternal and child morbidity. Screening for diabetic retinopathy (DR) is important because patients who develop DR have no symptoms until macular edema and/or proliferative diabetic retinopathy (PDR) are already present. The aim of this study was to determine the early retinal findings of GDM. MATERIAL AND METHODS: This study was conducted in a tertiary research center. We conducted a prospective cross-sectional study with 3 groups: Group 1 consisted of 36 pregnant women with GDM, Group 2 consisted of 24 healthy pregnant women, and Group 3 consisted of 38 healthy non-pregnant women of reproductive age. Spectralis optical coherence tomography (OCT) was used for the assessment. Macular, choroid, and retinal nerve fiber layer (RNFL) thicknesses were evaluated in patients with GDM and comparisons were made among pregnant women with GDM, healthy pregnant women, and healthy non-pregnant women for these parameters. RESULTS: The nasal part of the RNFL was significantly thinner in the GDM group than in the healthy pregnant group. None of the patients had retinopathy or macular edema at the time of examination. CONCLUSIONS: Decreased nasal part of RNFL thickness may be the first retinal change in patients with GDM. Our study suggests that OCT should be performed for the patients with GDM for detection of early retinal changes associated with GDM.