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Journal of Istanbul Faculty of Medicine
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ISSN (Print) 1305-6433 - ISSN (Online) 1305-6441
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  • EVALUATION OF MITOCHONDRIAL DNA MUTATIONS IN SIX FAMILIES BY RESEQUENCING
           ARRAY

    • Authors: Guyem KOLBAŞI DEMİRCİOĞLU; Sezen GÜNTEKİN ERGÜN, Kıvılcım GÜCÜYENER, Ferda E. PERÇİN, Mehmet Ali ERGUN
      Abstract: Objective: Human mitochondrial DNA is a circular, double stranded molecule which is inherited through maternal lineage. Point mutations in tRNA, rRNA or protein coding genes and structural rearrangements such as partial deletions or duplications can cause mitochondrial disorders. The prevalence of mitochondrial diseases is estimated to be 1/5000 worldwide. For the analysis of mtDNA mutations, Sanger sequencing, Southern blot, long and quantitative PCR, Resequencing Array and next-generation sequencing methods can be used. In this study, we analysed whole mitochondrial genomes of six children (along with their mothers) who were admitted to Gazi University Hospital with symptoms suggestive of mitochondrial disease. Materials and Methods: After the extraction of genomic DNA from six children and their mothers, mtDNA resequencing with the analysis of obtained data was performed. In order to determine whether one of the mutations found in Patient 4 was homoplasmic or heteroplasmic, PCR and RFLP techniques were also used. Results: Among six patients included in this study group, none of the variants detected could be attributed to any mitochondrial diseases, except the pathogenic mutation detected in Patient 4. The m.3460 G>A mutation detected in Patient 4 was located in the MT-ND1 gene that was known to be responsible for LHON. This mutation detected in Patient 4 was also detected both in his mother and sister with homoplasmic state. The lack of clinical findings in his mother and sister was thought to be due to decreased penetrance of the disease in females and modifying genes in nuclear genome. Conclusion: Screening of mtDNA using resequencing method could provide fast, effective and more reliable results in the diagnosis of mitochondrial diseases. Also, currently, the NGS technology analysis of nuclear DNA along with mtDNA will provide more reliable results in diagnosis of mitochondrial diseases, thus allowing more accurate genotype-phenotype correlation.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • ISOLATED ABERRANT RIGHT SUBCLAVIAN ARTERY: SHOULD INVASIVE INTERVENTION BE
           RECOMMENDED IN THE ERA OF NONINVASIVE PRENATAL TESTS'

    • Authors: Tuğba SARAÇ; Selen GÜRSOY ERZİNCAN, Lutfiye UYGUR, Çiğdem KUNT İŞGÜDER, Savcı Bekir TELEK, Recep HAS, İbrahim KALELİOĞLU
      Abstract: Objective: An aberrant right subclavian artery (ARSA) is an aortic arch anomaly isolated or associated with other ultrasound markers and/or congenital anomalies. This study aimed to evaluate the necessity of invasive prenatal tests (PIT) in cases with isolated ARSA (iARSA) in prenatal sonography. Materials and Methods: The presence of ARSA was evaluated retrospectively in 7690 fetuses who underwent a second-trimester ultrasonography evaluation between March 2015 and February 2021. PIT was recommended for patients with non-iARSA. cfDNA test (including 22q11.2 microdeletion/duplication syndrome (MMS) or PIT was suggested for patients with iARSA. Results: The mean week of gestation was 20.26±3.93 in 95 fetuses diagnosed with ARSA. Of the fetuses, fourty-two (44%) had iARSA, and 53 (56%) had additional findings. No chromosomal abnormality was found in any of the isolated cases. Trisomy 21 in 14, Trisomy 18 in one, 47,XX,+i(9)(p10) in one of 53 were found in non-isolated cases. Additional abnormalities and/or soft ultrasound markers were accompanied in all fetuses with chromosomal abnormalities. Conclusion: When iARSA is detected in prenatal ultrasonography, cfDNA testing may be sufficient, including 22q11.2 MMS. However, PIT should be recommended in the presence of structural abnormalities, soft ultrasound markers, or increased risk in the antenatal screening test.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • ASSOCIATING eNOS GENE VARIANTS WITH COVID-19 SUSCEPTIBILITY IN THE TURKISH
           POPULATION

    • Authors: Naci ŞENKAL; Yasemin OYACI, Timurhan CEBECİ, Hilal KONYAOĞLU, Murat KÖSE, Mustafa ÖNEL, Alpay MEDETALİBEYOĞLU, Gözde YEŞİL SAYIN, Mustafa PEHLİVAN, Sacide PEHLİVAN, Ümmuhan İŞOĞLU-ALKAÇ, Tufan TÜKEK
      Abstract: Objective: COVID-19 is a serious respiratory and vascular disease that impairs the protective function of the endothelial barrier. Endothelial nitric oxide synthase (eNOS), the most important isoform for nitric oxide (NO) production, is mostly expressed in endothelial cells. Therefore, this study aims to evaluate whether eNOS G894T and variable tandem repeat number (VNTR) functional variants show predisposition to developing COVID-19. Materials and Methods: The study includes a total of 384 subjects (284 COVID-19 patients and 100 healthy controls). Two eNOS gene variants (G894T and VNTR) were genotyped using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods, with the results being evaluated using statistical methods. Results: A significant association has been identified between eNOS G894T and COVID-19. For the eNOS G894T variant, the T/T genotype (p=0.035) and T allele carriers (p=0.030) appear to have an increased risk of developing COVID-19. The eNOS G894T G/G genotype (p=0.030) was more common in the control group compared to the patient group. No significant difference was found between groups regarding the eNOS VNTR genotype and allele frequencies (p˃0.05). The genotypes of the patient and control groups for these variants were in Hardy-Weinburg equilibrium (HWE). Conclusion: These results provide evidence supporting the hypothesis that the eNOS G894T variant is associated with an increased risk of developing COVID-19 in the Turkish population. These findings may lead to the emergence of new treatment options. Further research is required to understand the molecular mechanisms involved in the pathogenesis of the disease.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • PREVALENCE AND ASSOCIATED FACTORS OF ADVERSE EFFECTS IN CHILDREN AND
           ADOLESCENTS TREATED WITH SELECTIVE SEROTONIN REUPTAKE INHIBITORS: A CHART
           REVIEW STUDY

    • Authors: Hanım Hülya ALINAY; Ali KARAYAĞMURLU, Murat COŞKUN
      Abstract: Objective: This study aims to examine the prevalence and associated clinical and sociodemographic factors of adverse effects in medication among naïve young subjects who received selective serotonin reuptake inhibitor (SSRI) monotherapy. Material and Methods: The medical records of 85 patients who had received SSRI monotherapy in a university hospital’s child and adolescent psychiatry clinic were reviewed. The subjects who met the inclusion criteria were included in the study. Results: A total of 67 subjects (10.82±3.63 years) were included. More than half (n=39, 58.9%) developed at least one adverse effect possibly associated with SSRI treatment, with psychic (n=25, 37.3%) and autonomic (n=20, 29.9%) adverse effects as well as behavioral activation (n=13, 19.4%) being the most frequently reported. Medication was discontinued in 13 subjects (19.4%) due to adverse effects, with behavioral activation (6 out of 13 subjects) being the most frequent reason for discontinuation. The development of behavioral activation was significantly associated with younger age, diagnosis of obsessive compulsive disorder in the subjects, and psychiatric history in the subjects’ fathers (p value<0.05). Conclusions: Despite the fact that SSRIs are generally safe and well-tolerated in young subjects, adverse effects may be frequent, and medication discontinuation may be required under some conditions. Thus, clinicians treating young subjects should be cautious, particularly about the development of behavioral activation. They should also be mindful of the clinical and sociodemographic factors associated with the adverse effects that may arise during SSRI treatment.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • EVALUATION OF THE TREATMENT EFFICACY OF TIGECYCLINE AND REISHI SHIITAKE
           MAITAKE MUSHROOM EXTRACT IN MICE WITH THE VISCERAL LEISHMANIASIS MODEL

    • Authors: Özden BORAL; Deniz Gözde ÇELİK, Halim İŞSEVER
      Abstract: Objective: Visceral leishmaniasis (VL) is an infection that can be fatal if left untreated. Treatment of VL is becoming increasingly difficult due to the development of resistance to some drugs used. We aimed to investigate the efficacy of tigecycline (Tig) and Reishi-Shiitake-Maitake (RSM) mushroom extract alone and in combination in BALB/c mice infected with the Leishmania donovani strain (ATCC 30030). Materials and Methods: To compare the treatment efficacy, the mice that were treated with amphotericin B (AMB) were used as the control group. BALB/c mice (n=40) were intravenously inoculated in the lateral vein of the tail with 107 stationary-phase L. donovani promastigotes in 100 μL of PBS. BALB/c mice were divided into 5 groups of 8. Tig group received 3.7 mg/kg tigecycline intraperitoneally for 5 days, RSM group received 10 mg/ kg RSM extract by oral gavage for 5 days while Tig+RSM group received the same doses of both drugs via the same routes. Also, the AMB group received 15mg/kg amphotericin B by oral gavage for 5 days. The spleen and liver of all mice that were sedated with ketamine were collected on the 12th day. Parasite load was determined by Leishman Donovan Unit (LDU) and quantitative RT-PCR. Results: When all groups were statistically evaluated according to LDU and RT-PCR findings, the lowest value was obtained in the AMB group compared to the value in the control group, while the second lowest value was obtained in the Tig+RSM group. The data obtained in the Tig+ RSM group were significantly lower macrothan the data in other groups, except for the AMB group. Conclusion: Our study suggested that the use of RSM extract together with tigecycline may be an alternative in the treatment of VL. Further studies using different doses and routes of administration are needed to evaluate the efficacy of this combination.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • TURKISH DIALYSIS HEALTHCARE PROVIDERS’ PSYCHOLOGICAL RESPONSE TO
           COVID-19

    • Authors: İrmak POLAT; Mehmet Sukru SEVER, Erol DEMİR, Halil YAZICI, Serkan Kubilay KOÇ, Rabia PAPİLA, Mine ÖZKAN
      Abstract: Objective: COVID-19 has been a stressful experience for healthcare providers (HCPs) and created additional distress for dialysis HCPs due to patients’ higher risk of infection, symptom severity, and death. This study aims to investigate Turkish dialysis HCPs’ levels of psychological difficulties during COVID-19’s initial outbreak. Materials and Methods: The study has recruited physicians, nurses, and healthcare workers in dialysis centers. The participants completed an online survey that includes the screening questionnaire, Depression Anxiety Stress Scale-21 (DASS21), and Multidimensional Scale of Perceived Social Support (MSPSS). The study conducts the chi-square test, Fisher’s exact test, Mann-Whitney U test, Kruskal Wallis H test, Spearman correlation, and linear regression analyses. Results: The study involves 953 respondents, with nurses making up the majority (n=465, 48.8%), followed by healthcare workers (n=402; 42.2%) and physicians (n=86; 9%). HCPs’ most significant concerns were getting infected with COVID-19 and transmitting the disease to their loved ones. Single participants, those without children, those who had trouble finding equipment, and those worried about being able to find equipment in the future, being in contact with COVID-19 (+) people, those whose tobacco and alcohol use increased, and those who declared sleep, appetite, and/or somatic problems had higher DASS-21 scores. When compared respectively to healthcare workers and physicians, nurses were found to be more worried about getting COVID-19 (94.6% compared to 90.6% and 84.7%; p < 0.001), experience equipment shortages (52.9% compared to 29.4% and 26.3%; p<0.001), have sleep (62.2% compared to 43.5% and 34%; p<0.001) and somatic problems (58.4% compared to 50% and 28.2%; p<0.001), and higher DASS-21 scores (Range=5-21 compared to 3-15 and 0-12; p<0.001). Conclusion: Worries and lifestyle changes associated with the outbreak are seen to have been be related to psychological difficulties. An adequate level of knowledge, self-protection, and social support are essential issues for HCPs. While this study recommends that HCPs express and share their worries, institutions should also focus on the psychological status of their staff and provide immediate interventions.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • EXPLORING MITOMIRS IN BREAST CANCER: AN IN-VITRO STUDY OF THEIR EMERGING
           ROLES

    • Authors: Pervin Elvan TOKGÜN; Ayşe Gaye TOMATIR
      Abstract: Objective: Breast cancer is associated with a 5% genetic predisposition in women. Mitochondria play a role in important cellular events such as metabolism, cell death, and inflammation. Recent studies have highlighted precursor micro-RNA (pre-miRNA) to be located in mitochondria as well as mature miRNA. This study aims to reveal the occurrence of mitochondrial miRNA (mitomiR) in breast cancer cells. Materials and Methods: The study has prepared the mitochondrial fractions using the magnetic-activated cell sorting (MACS) method and performed small RNA (sRNA) sequencing. Results: The study has identified known and novel mitomiR sequences aligned to the mitochondrial genome. Conclusion: Identifying new mitomiRs can provide significant contributions and illuminate the molecular mechanism underlying mitomiR biogenesis.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • REGIONAL INVOLVEMENT IN LEFT VENTRICULAR STRAIN IN PATIENTS RECOVERED FROM
           COVID-19 PNEUMONIA

    • Authors: Ekrem Bilal KARAAYVAZ; Berat ENGİN, Pelin KARACA ÖZER, Zeynep Gizem DEMİRTAKAN, Elif AYDUK GÖVDELİ, Turker DEMIRTAKAN, Derya BAYKIZ, Alpay MEDETALİBEYOĞLU
      Abstract: Objective: COVID-19 patients with cardiovascular involvement have been shown to have a worse prognosis compared to those without cardiovascular compromise. This study aimed to investigate whether left ventricular (LV) global and regional strain is impaired in patients with COVID-19 with or without pneumonia after discharge. Materials and Methods: Seventy-eight consecutive COVID-19 patients diagnosed by PCR test were enrolled in this cross-sectional study during their first follow-up visit to an outpatient clinic. All patients underwent two-dimensional echocardiography and speckle tracking echocardiography (STE) at the first follow-up visit. The patients were divided into two groups with or without pneumonia, and they were compared with the healthy control group. Results: A total of 123 subjects were included in the study (78 with COVID-19 and 45 in the control group). Admission and follow-up hs-troponin-T concentrations were similar in both the control group and patients with varying severity of COVID-19. LV ejection fraction (EF) was similar in all groups. However, LV global longitudinal strain (GLS) was significantly lower in subjects with pneumonia compared to the control group and subjects without pneumonia. Regional strain analysis showed that subjects with pneumonia had significantly lower strain values at mid-anterior, mid-anteroseptal, apical-inferior, apical-lateral, and apex regions than subjects without pneumonia or the control group. Conclusion: LV GLS and the regional strain were significantly impaired in COVID-19 patients with pneumonia compared to those without pneumonia or in to control group. This finding indicates that COVID-19 subjects with pneumonia should undergo strain measurement to detect concealed LV involvement.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • CHARACTERISTICS AND SURVIVAL OF BRAIN METASTASIS FROM TWO RADIORESISTANT
           TUMORS, MALIGNANT MELANOMA AND RENAL CELL CARCINOMA: A SINGLE RADIOTHERAPY
           CENTER STUDY

    • Authors: Zümrüt BAHAT; Özlem AYNACI, Vildan ALTUNAYOGLU CAKMAK, Ertuğrul ÇAKIR, Mustafa KANDAZ, Serdar ÖZKÖK
      Abstract: Objective: Malignant melanoma (MM) and renal cell carcinoma (RCC) are rare radioresistant tumors that often metastasize to the brain. Because of their rarity, studies on brain metastatic RCC and MM are limited. We aimed to outline the characteristics of brain metastasis (BM) patients from RCC and MM and analyze the potential prognostic factors for survival. Materials and Methods: This is a retrospective-observational study using data from patients admitted to a radiotherapy (RT) center of a university hospital between 1998-2020. Clinicopathological characteristics, treatment details, and outcome results were analyzed. Univariate and multivariate survival analyses were performed. Results: Among a total of 14,603 patients treated in our center in the study period, only 52 (0.004%) were BM cases from MM or RCC. Forty patients had complete data (median age at diagnosis of MM or RCC-related BM: 57.7; females: 25%; MM in 52.5% and RCC in 47.5%). The time between primary diagnosis and first extracranial metastases was weakly correlated with the time between diagnosis of extracranial metastasis and BM (r=0.405, p=0.021). Among the potential prognostic factors on survival [age, sex, older vs younger age group, primary diagnosis (MM vs RC), presence of extracranial metastasis, number of BM, location of BM, presence of gross total resection, dose of RT, completion of prescribed RT, field of RT], none were independently associated with survival. Conclusion: Our findings suggest that when MM or RCC patients develop brain metastasis, survival is limited without any favorable prognostic factor belonging to the patient, the tumor, or the preference of the treatment.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • THE EFFECT OF miR-34a-5p ON OVEREXPRESSED AML ASSOCIATED GENES

    • Authors: Murat KAYA; Ilknur SUER
      Abstract: Objective: Acute myeloid leukemia (AML) is a deadly type of leukemia. The expression of AML-related genes may be altered not only by genetic changes but also by various epigenetic factors such as microRNAs (miRNAs). The expression levels of many genes can be altered by miRNAs. The detection of miRNA’s target genes is critical for an understanding of the disease’s molecular mechanism. In this study possible target genes of miR-34a-5p in AML were determined and the effect of the relationship between miR-34a-5p and target genes on the cancer process was investigated. Materials and Methods: Leukemia Gene and Literature Database web tool (http://soft.bioinfo-minzhao.org/lgl/) includes a useful leukemia gene and literature da. There are more than 600 AML-related genes on this database. In the present study, in order to define the potential target genes of miR-34a-5p on the database, we used miRDB tool and then confirmed the findings using miRWalk, miRTarbase, Tarbase and miRNet tools. Defined miR-34a-5p AML related genes were verified by the DisGeNET platform. A Protein-Protein Interaction (PPI) network analysis of the genes was conducted using several bioinformatics tools. The effect of miR-34a-5p on cell proliferation was investigated by transfecting mimic miR-34a-5p into HL60 and NB4 cells. The mRNA expressions of NOTCH2, IGF1R, SKP2 and CDC25A genes were investigated in miR-34a-5p transfected NB4 and HL60 cells and control groups. Results: Using bioinformatics tools we determined 44 AMLrelated genes that could be targeted by miR-34a-5p. According to our in vitro study results statistically significant suppression of proliferation was observed in miR-34a-5p transfected cells (48h HL60 cells p=0.00011; NB4 cells p=0.0031 and 96h HL60 cells p=0.00013; NB4 p=0.00018). It was also found that NOTCH2, IGF1R, SKP2 and CDC25A mRNA expressions were down regulated in miR-34a-5p mimic-transfected HL60 cells (p=0.003; p=0.02; p=0.01; p=0.0009 respectively) and NB4 cells (p=0.02; p=0.02; p=0.01; p=0.0007 respectively) compared to the control groups. Conclusion: miR-34a-5p may inhibit AML cell proliferation by targeting many genes like NOTCH2, IGF1R, SKP2 and CDC25A. The results of our study indicate that appropriate bioinformatics tools and in vitro methods can successfully be used together when investigating the relationship between miRNAs and target genes. Further studies are required to determine the detailed relationship between these genes and miR-34a-5p.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • AN EVALUATION OF RETROSPECTIVE RESULTS DETECTED IN THE HOSPITAL INFECTION
           RESEARCH LABORATORY

    • Authors: Niyousha Matloobi AGHDAM; Gülseren AKTAŞ
      Abstract: Objective: Hospitals are a potential source of infection risk during healthcare delivery. Since vancomycin-resistant enterococci (VRE) and carbapenemase producing Gram-negative rods cause persistent colonization and multi-drug resistant bacterial infections, they are important in nosocomial infections. In this study, we aimed to retrospectively evaluate rectal swab samples of patients hospitalized in the clinics in terms of VRE and carbapenem- resistant (CR) Gram-negative rods as nosocomial infection agents between 1st January 2020 and 31st December 2020. Materials and Methods: Standard clinical laboratory methods were used to isolate and identify CR Gram-negative rods and VRE from rectal swab samples of hospitalized patients sent to our Hospital Infection Research Laboratory. Results: There was growth in 777 (28.9%) of 2688 samples examined. Of the bacteria that grew, 627 (80.7%) were defined as VRE, and 150 (19.3%) as Gram-negative rods resistant to carbapenem. Seventy-five of these were defined as CR K. pneumoniae: 7 as CR K. oxytoca: 26 as CR Enterobacter species: 2 as CR E. coli: and 40 as CR Acinetobacter species. Vancomycin-resistant enterococci were detected most frequently in the internal medicine ward (56.3% - 353/627) and pediatric intensive care-neonatal ward (37.6% - 236/627). In pediatric services, 146 of total 296 bacteria isolated were identified as VRE. Conclusion: With the surveillance studies carried out in the control of hospital infections, each health institution determines the microorganisms that make up its own hospital flora, their resistance status and their distribution. It is thought that the data we obtain will contribute to the infection control processes of the hospitals.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
  • DETERMINING THE IMPORTANCE OF GLYCEMIC VARIABILITY IN GESTATIONAL DIABETES
           MELLITUS USING VARIOUS TECHNIQUES

    • Authors: Nida ÖZTOP; Ayşe KUBAT ÜZÜM, Selda ÇELİK, Cemile İDİZ, Yıldız TUTUNCU, Elif BAĞDEMİR, Nevin DİNÇCAĞ
      Abstract: Objective: The study aims to determine glycemic variation in patients with gestational diabetes mellitus (GDM) and to evaluate the effect on the fetal growth using a continuous glucose monitoring system (CGMS) and to investigate the correlation between glucose variation through biomarkers including HbA1c, fructosamine (FRM), and 1.5-Anhydroglucitol (1.5-AG). Materials and Methods: The study involves 31 women with GDM at gestational week ≥35 who’d only had diet therapy. Blood glucose levels were monitored for three consecutive days using CGMS to evaluate mean blood glucose levels and mean absolute difference (MAD). Self-monitoring of blood glucose (SMBG) was required from the patients while having the CMGS on their body. Blood samples were collected to measure serum 1.5-AG, HbA1c, and FRM. Results: The mean levels were HbA1c=5.0±0.3%, FRM=2.1±0.2 μmol/L, 1.5-AG=17.0±4.9 ng/ml, and 3-day average max-min glucose range=131.1±22.5 and 54.7±11.6 mg/dl (MAD=6.7±3.1%). The mean glucose levels measured using SMBG and CGMS were similar (82.9±10.2 vs 86.1±10.3 mg/dL). No correlation occurred between CMGS and biomarkers. The baby weight at birth and head circumference was determined to be lower for patients with glucose fluctuations. Conclusion: Biomarkers do not reflect glycemic fluctuation, and regular SMBG is required to achieve the desired glucose level, even in diet-regulated GDM. Lower head circumference and birth weight were determined in GDM mothers with high glycemic fluctuations, and CGMS may be an alternative method despite its cost and application difficulties.
      PubDate: Tue, 31 Jan 2023 00:00:00 +030
       
 
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