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The high recurrence rate of hepatocellular carcinoma (HCC) and poor prognosis after medical treatment reflects the necessity to improve the current chemotherapy protocols, particularly drug delivery methods. Development of targeted and efficient drug delivery systems (DDSs), in all active, passive and stimuli-responsive forms for selective delivery of therapeutic drugs to the tumour site has been extended to improve efficacy and reduce the severe side effects. Recent advances in nanotechnology offer promising breakthroughs in the diagnosis, treatment and monitoring of cancer cells. In this review, the specific design of DDSs based on the different nano-particles and their surface engineering is discussed. In addition, the innovative clinical studies in which nano-based DDS was used in the treatment of HCC were highlighted.

SMA (spinal muscular atrophy) is an autosomal recessive neuromuscular disease that causes muscle atrophy and weakness. SMA is diagnosed by a homozygous deletion in exon 7 of the SMN1 gene. However, mutations in genes located in the SMA region, such as SMN2 , NAIP, SERF1, and GTF2H2, may also contribute to the severity of the disease. Within our study's scope, 58 SMA patients who applied in 2018-2021 and 40 healthy controls were analyzed. The study retrospectively included the SMN1 and SMN2 copy numbers previously determined by the MLPA method. Then, NAIP gene analyses with the multiplex PCR method and GTF2H2 gene analyses with the RFLP method were performed. There was a significant correlation ( p  = 0.00001) between SMN2 copy numbers and SMA subtypes. Also, the NAIP gene ( p  = 0.01) and the GTF2H2 gene ( p  = 0.0049) revealed a significant difference between healthy and SMA subjects, whereas the SMA subtypes indicated no significant differences. We detected a significant correlation between clinical subtypes and HFMSE scores in 32 pediatric SMA patients compared ( p  = 0.01). While pediatric patients with GTF2H2 deletions demonstrated higher motor functions, and those with NAIP deletions demonstrated lower motor functions. In this study, we examined the relationship between NAIP and GTF2H2 , called SMN region modifier genes, and the clinical severity of the disease in Turkish SMA patients. Despite its small scale, this research will benefit future investigations into the pathogenesis of SMA disease.

Artificial intelligence (AI) platforms have emerged as pivotal tools in genetics and molecular medicine, as in many other fields. The growth in patient data, identification of new diseases and phenotypes, discovery of new intracellular pathways, availability of greater sets of omics data, and the need to continuously analyse them have led to the development of new AI platforms. AI continues to weave its way into the fabric of genetics with the potential to unlock new discoveries and enhance patient care. This technology is setting the stage for breakthroughs across various domains, including dysmorphology, rare hereditary diseases, cancers, clinical microbiomics, the investigation of zoonotic diseases, omics studies in all medical disciplines. AI's role in facilitating a deeper understanding of these areas heralds a new era of personalised medicine, where treatments and diagnoses are tailored to the individual's molecular features, offering a more precise approach to combating genetic or acquired disorders. The significance of these AI platforms is growing as they assist healthcare professionals in the diagnostic and treatment processes, marking a pivotal shift towards more informed, efficient, and effective medical practice. In this review, we will explore the range of AI tools available and show how they have become vital in various sectors of genomic research supporting clinical decisions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Aim: Chromosomal analysis is a laboratory technique used to examine the chromosomes of an individual, offering insights into chromosome numbers, structures, and arrangements to diagnose and comprehend genetic diseases. This retrospective study provides a comprehensive understanding of the distribution by indications in a large cohort of 14,242 patients and the frequency of chromosomal abnormalities in different clinical populations., Method: The study examined various indications for karyotype evaluation, with recurrent pregnancy loss being the most common indication, followed by intellectual disability, dysmorphic features, congenital anomalies, and developmental delay., Results: The overall chromosomal abnormality rate was found to be 5.4%, with numerical abnormalities accounting for the majority of cases (61.7%). Trisomies, particularly trisomy 21, were the most frequent numerical abnormalities. In terms of structural abnormalities, inversions and translocations were the most commonly identified. The rates of chromosomal anomalies varied in specific indications such as amenorrhea, disorders of sex development, and Turner syndrome. The study also highlighted significant differences between males and females in the presence of chromosomal abnormalities across certain indications. Males exhibited a higher incidence of chromosomal abnormalities in cases of Down syndrome and infertility, whereas females showed higher abnormalities in terms of recurrent pregnancy loss., Conclusion: While this study provides valuable insights into the frequency and distribution of chromosomal abnormalities, it has limitations, including its retrospective design and reliance on data from a single medical genetics department. Nevertheless, the findings emphasize the importance of karyotype analysis in diagnosing chromosomal disorders and providing appropriate management, while also pointing to potential gender-related variations in chromosomal abnormalities that warrant further investigation., (© 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Cefiderocol is generally active against carbapenem-resistant Klebsiella spp. (CRK) with higher MICs against metallo-beta-lactamase producers. There is a variation in cefiderocol interpretive criteria determined by EUCAST and CLSI. Our objective was to test CRK isolates against cefiderocol and compare cefiderocol susceptibilities using EUCAST and CLSI interpretive criteria., Methods: A unique collection ( n  = 254) of mainly OXA-48-like- or NDM-producing CRK bloodstream isolates were tested against cefiderocol with disc diffusion (Mast Diagnostics, UK). Beta-lactam resistance genes and multilocus sequence types were identified using bioinformatics analyses on complete bacterial genomes., Results: Median cefiderocol inhibition zone diameter was 24 mm (interquartile range [IQR] 24-26 mm) for all isolates and 18 mm (IQR 15-21 mm) for NDM producers. We observed significant variability between cefiderocol susceptibilities using EUCAST and CLSI breakpoints, such that 26% and 2% of all isolates, and 81% and 12% of the NDM producers were resistant to cefiderocol using EUCAST and CLSI interpretive criteria, respectively., Conclusions: Cefiderocol resistance rates among NDM producers are high using EUCAST criteria. Breakpoint variability may have significant implications on patient outcomes. Until more clinical outcome data are available, we suggest using EUCAST interpretive criteria for cefiderocol susceptibility testing.

Purpose: This paper aimed to evaluate the effects of the COVID-19 pandemic on healthcare-associated infections (HAIs), antibiotic resistance and consumption rates in intensive care units (ICUs) of a tertiary care university hospital., Patients and Methods: Between 1 January 2018 and 31 December 2021, adult patients diagnosed with HAIs in ICUs were investigated retrospectively. Patients were divided into pre-pandemic (2018-2019) and pandemic periods (2020-2021). Antibiotic consumption index was calculated via using the formula of (total dose (grams)/defined daily dose (DDD) x total patient days) x1000. A p value below 0.05 was accepted as statistically significant., Results: The incidence of HAIs (per 1000 patient days) in the ICU of COVID-19 patients was 16.59, while it was 13.42 in the other ICUs during the pandemic period (p=0.107). The bloodstream infection (BSI) incidence was 3.32 in the pre-pandemic period and 5.41 in the pandemic period in ICUs other than the ICU of COVID-19 patients (p<0.001). In the pandemic period, the BSI incidence rate was significantly higher in the ICU of COVID-19 patients than in the other ICUs (14.26 vs 5.41, p<0.001). Central venous catheter bloodstream infections incidence rate was 4.72 in the pre-pandemic and 7.52 in the pandemic period in ICUs other than the ICU of COVID-19 patients (p=0.0019). During the pandemic period, the bacteraemia episode rates of Acinetobacter baumannii (5.375 vs 0.984, p<0.001), Enterococcus spp . (1.635 vs 0.268, p<0.001) and Stenotrophomonas maltophilia (3.038 vs 1.297, p=0.0086) in the ICU of COVID-19 patients were significantly found higher than others. The extended-spectrum beta-lactamase (ESBL) positivity rates for Klebsiella pneumoniae and Escherichia coli were 61% and 42% in the pre-pandemic period; 73% and 69% in the pandemic period in ICUs other than the ICU of COVID-19 patients (p>0.05). In the pandemic period, the ESBL positivity rates for K. pneumoniae and E. coli were 83% and 100% in the ICU of COVID-19 patients, respectively. Meropenem (p<0.001), teicoplanin (p<0.001) and ceftriaxone (p<0.001) consumptions were increased while ciprofloxacin (p=0.003) consumption was decreased in all ICUs after the pre-pandemic period., Conclusions: BSI and CVCBSI incidence rates were significantly increased in all ICUs after the COVID-19 pandemic in our hospital. Bacteraemia episode rates of A. baumannii , Enterococcus spp. and S. maltophilia in ICU of COVID-19 patients were significantly found higher than others. In addition, meropenem, teicoplanin and ceftriaxone consumptions were increased in all ICUs after the COVID-19 pandemic., Competing Interests: Conflict of interest All authors declare that they have no competing interests.

Extracellular vesicles (EVs) are produced by various cells and exist in most biological fluids. They play an important role in cell-cell signaling, immune response, and tumor metastasis, and also have theranostic potential. They deliver many functional biomolecules, including DNA, microRNAs (miRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA), lipids, and proteins, thus affecting different physiological processes in target cells. Decreased immunogenicity compared to liposomes or viral vectors and the ability to cross through physiological barriers such as the blood-brain barrier make them an attractive and innovative option as diagnostic biomarkers and therapeutic carriers. Here, we highlighted two types of cells that can produce functional EVs, namely, mesenchymal stem/stromal cells (MSCs) and regulatory T cells (Tregs), discussing MSC/Treg-derived EV-based therapies for some specific diseases including acute respiratory distress syndrome (ARDS), autoimmune diseases, and cancer., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The continual course of the pandemic points to the importance of studies on the rate and durability of protective immunity after infection or vaccination., Aims: In this study, we aimed to monitor anti-nucleocapsid (N) and anti-spike (S) antibodies against SARS-CoV-2 nearly 9 months duration after infection., Methods: Anti-nucleocapsid (N) (at 11-15-20-29-38 weeks) and anti-spike antibodies (at 11 and 38 weeks) against SARS-CoV-2 were monitored during 38 weeks after the initial symptoms of COVID-19., Results: Of 37 cases between 18 and 57 years old, 54% were women. The findings showed that anti-N antibodies decreased significantly after the 15th week (between 15 and 20 weeks, p = 0.016; 20-29 weeks, p = 0.0009; and 29-38 weeks, p = 0.049). At the 38th week, mean antibody levels decreased 35% compared to the 11th week, and 8% of the cases turned negative results. Anti-N antibody average level was 56.48 on the 11th week (the cut-off index threshold ≥ 1). It was estimated statistically that it would decrease to an average of 20.48 in weeks 53-62. In females, average antibody levels of all measurements were lower than males (p > 0.05). Anti-S antibody levels 14% increased at 38th week compared to 11th week (quantitative positivity threshold ≥ 0.8 U/ml), and no cases were negative at 38th week., Conclusions: Patients had ≥ 90% positivity after at least 9 months of symptoms, both anti-N and anti-S antibodies. In all samples, both anti-N and anti-S antibody levels were lower in females. The findings suggest that the quantitative values of anti-S antibodies remained high for at least 9 months and could provide protection., (© 2021. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Introduction. Aminoglycosides are used for the treatment of carbapenemase-producing Klebsiella pneumoniae (CPK) infections. 16S rRNA methyltransferases (RMTs) confer resistance to all aminoglycosides and are often cocarried with NDM. Hypothesis/Gap Statement. There is a dart of studies looking at the aminoglycoside resistance mechanisms for invasive CPK isolates, particularly in OXA-48 endemic settings. Aim. We aimed to determine the prevalence of RMTs and their association with beta lactamases and MLSTs amongst aminoglycoside-resistant CPK bloodstream isolates in an OXA-48 endemic setting. Methodology. CPK isolates ( n =181), collected as part of a multicentre cohort study, were tested for amikacin, gentamicin and tobramycin susceptibility using custom-made sensititre plates (GN2XF, Thermo Fisher Scientific). All isolates were previously subjected to whole-genome sequencing. Carbapenemases, RMTs, MLSTs and plasmid incompatibility groups were detected on the assembled genomes. Results. Of the 181 isolates, 109(60 %) were resistant to all three aminoglycosides, and 96 of 109(88 %) aminoglycoside-resistant isolates carried an RMT (85 ArmA, 10 RmtC, 4 RmtF1; three isolates cocarried ArmA and RmtC). Main clonal types associated with ArmA were ST2096 (49/85, 58 %) and ST14 (24/85, 28 %), harbouring mainly OXA-232 and OXA-48 +NDM, respectively. RmtC was cocarried with NDM (5/10) on ST395, and NDM +OXA-48 or NDM +KPC (4/10) on ST14, ST15 and ST16. All RMT producers also carried CTX-M-15, and the majority cocarried SHV-106, TEM-150 and multiple other antibiotic resistance genes. The majority of the isolates harboured a combination of IncFIB, IncH and IncL/M type plasmids. Non-NDM producing isolates remained susceptible to ceftazidime-avibactam. Conclusion. Aminoglycoside resistance amongst CPK bloodstream isolates is extremely common and mainly driven by clonal spread of ArmA carried on ST2096 and ST14, associated with OXA-232 and OXA48 +NDM carriage, respectively.

Hair loss is a widespread concern in dermatology clinics, affecting both men's and women's quality of life. Hair loss can have many different causes, which are critical to identify in order to provide appropriate treatment. Hair loss can happen due to many variables, such as genetic factors or predisposition, vitamin and mineral deficiencies, skin problems, hair growth disorders, poor diet, hormonal problems, certain internal diseases, drug use, stress and depression, cosmetic factors, childbirth, and the chemotherapy process. Treatment for hair loss varies depending on the type of alopecia, deficiency, or excess of structures such as vitamins and minerals, and also on hair and skin structure. The Mediterranean diet is characterized by low amounts of saturated fat, animal protein, and high amounts of unsaturated fat, fiber, polyphenols, and antioxidants. The main nutrients found in the Mediterranean Diet are rich in antioxidant, anti-inflammatory components. It also has an important place in hair loss treatment, since recently treatment strategies have included polyphenols and unsaturated oils more and more frequently. The goal of this work was to review published articles examining alopecia and its types, the many micronutrients that affect alopecia, and the role of the Mediterranean diet in alopecia. The literature shows that little is known about hair loss, nutritional factors, and diet, and that the data collected are conflicting. Given these differences, research into the function of diet and nutrition in the treatment of baldness is a dynamic and growing topic., (©2022 Pacini Editore SRL, Pisa, Italy.)

Epigenetics, defined as "hereditary changes in gene expression that occur without any change in the DNA sequence", consists of various epigenetic marks, including DNA methylation, histone modifications, and non-coding RNAs. The epigenome, which has a dynamic structure in response to intracellular and extracellular stimuli, has a key role in the control of gene activity, since it is located at the intersection of cellular information encoded in the genome and molecular/chemical information of extracellular origin. The focus shift of studies to epigenetic reprogramming has led to the formation and progressive importance of a concept called "nutriepigenetics", whose aim is to prevent diseases by intervening on nutrition style. Among the diet types adopted in the world, the renowned Mediterranean Diet (MD), being rich in unsaturated fatty acids and containing high levels of whole grain foods and large quantities of fruits, vegetables, and legumes, has shown numerous advantages in excluding chronic diseases. Additionally, the fact that this diet is rich in polyphenols with high antioxidant and anti-inflammatory properties has an undeniable effect in turning some cellular pathways against the disease. It is also apparent that the effects of polyphenols on the epigenome cause changes in mechanisms such as DNA methylation and histone acetylation/deacetylation, which have a regulatory effect on gene regulation. This review presents the effects of long-term consumption of nutrients from the MD on the epigenome and discusses the benefits of this diet in the treatment and even prevention of chronic diseases., (©2022 Pacini Editore SRL, Pisa, Italy.)

This study aims to investigate trends in bloodstream infections and their antimicrobial susceptibility profiles over 12 years in our hospital. This retrospective study was carried out in the Bursa Uludag University Hospital, Turkey, during 2008-2019. Blood cultures from patients were performed using BACTEC System. Isolates were identified with Phoenix System until 2018 and "matrix-assisted laser desorption ionization time-of-flight mass spectrometry" (MALDI-TOF MS) in 2019. Antibiotic susceptibility testing was performed with Phoenix System. Patient data came from the BD EpiCenter™ data management system. Escherichia coli was found to be the most common Gram-negative (11.6%), and coagulase-negative staphylococci were the most common Gram-positive (10.1%) monomicrobial growth. Overall, there was a significant increase in rates of extended-spectrum β-lactamase positive E. coli ( p = 0.014) and Klebsiella pneumonia ( p < 0.001), carbapenem-resistant E. coli ( p < 0.001), and K. pneumoniae ( p < 0.001) and colistin-resistant K. pneumoniae ( p < 0.001) and Acinetobacter baumannii ( p < 0.001) over 12 years. Carbapenem and colistin resistance has increased dramatically in recent years. We believe that regular monitoring of the distribution of pathogens and antibiotic susceptibility profiles, especially in intensive care units, can contribute to evidence for the increase in resistant microorganisms and help prevent their spread with antimicrobial stewardship and infection control policies., (© 2022 Nazmiye Ülkü Tüzemen et al., published by Sciendo.)

Ceftazidime-avibactam exhibits good in vitro activity against carbapenem resistant Klebsiella carrying OXA-48-like enzymes. We tested two hundred unique carbapenem resistant Klebsiella blood stream isolates (71% with single OXA-48-like carbapenemases, including OXA-48, n = 62; OXA-232, n = 57; OXA-244, n = 17; OXA-181, n = 5) that were collected as part of a multicentre study against ceftazidime-avibactam using Etest (bioMérieux, Marcyl'Étoile, France), 10/4 μg disc (Thermo Fisher) and Sensititre Gram Negative EURGNCOL Plates (Lyophilized panels, Sensititre, Thermo Fisher) with the aim of comparing the performances of the Etest and disc to that of Sensititre. Ceftazidime-avibactam MIC 50/90 was 2/>16 mg/L for the entire collection and was 2/4 mg/L for single OXA-48-like producers. Categorical and essential agreements between the Etest and Sensititre were 100% and 97%, respectively. Categorical agreement between the disc and Sensititre was 100%. Etest and 10/4 μg discs are suitable alternatives to Sensititre for ceftazidime-avibactam sensitivity testing for OXA-48-like producers., Competing Interests: Declaration of competing interest Dr. Paterson reports research grants from Merck, Pfizer and Shionogi. David Paterson has received honoraria for advisory board membership from Merck, Pfizer, Shionogi, GSK, QPex, Entasis, VenatoRx, BioMerieux, and Accelerate. Dr Harris has received research grants from Sandoz, Merck/MSD and Shionogi, speaker's fees from Pfizer and honoraria for advisory board membership from Merck and Sandoz, paid to the University of Queensland. All others have no conflict of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objective: Integrase strand transfer inhibitors (INSTIs) are currently the standard of practice for first-line HIV therapy for most patients. We evaluated the mutations associated with INSTI resistance in naive HIV-1 infected patients and treated them with antiretrovirals (ART)., Methods: The study, conducted in the 2018 - 2020 period, included 50 ART-naïve patients, 69 INSTI free ART-experienced patients, and 82 INSTI-experienced patients. INSTI resistance mutations were interpreted using the Stanford University HIVdb Program algorithm., Results: INSTI resistance was not detected in ART naïve patients. At least one INSTI resistance mutation was detected in 10% of the INSTI-free patients and 29% of the INSTI-treated patients. Major INSTI-mutations E138K, Y143R, S147G, Q148R, N155H, and E157Q were found in raltegravir. Additional mutations, E92Q, E138K, G140A, S147G, and Q148R were found in elvitegravir; E192Q, E138K/T, G140A/S, S147G, Q148H/R, N155H, E157Q were found in dolutegravir (DTG) experienced patients. According to all drug classes, drug resistance mutation prevalences were determined at the rate of 60%, 46%, and 46% in the RAL, EVG, and DTG groups, respectively., Conclusion: Our findings provide data for treatment and resistance management of INSTIs and may provide feedback for INSTIs resistance surveillance consensus-building efforts. In viral rebound under INSTI treatment, INSTI-resistant mutations follow typical INSTI resistance pathways and high resistance rates. INSTI resistance genotypic analysis should be considered before any DTG-based regimes can be initiated in the future, and reduced DTG susceptibility should be carefully monitored and investigated., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Due to the high prevalence of multi-drug resistant bacteria, combination therapy is an efficient choice for treatment of infections caused by highly resistant strains. In this study, the efficacy of ceftiofur plus danofloxacin combination was investigated against resistant Escherichia coli . The interaction between the two drugs was determined by checkerboard tests and time-kill assays. The combination was defined as bactericidal or bacteriostatic based on the minimum bactericidal concentration test results. Mutant prevention concentration test was used to evaluate the resistance tendency suppression potential of the combination. The combination had a synergistic effect against 83.00% of the isolates as verified by the checkerboard and time-kill assays. The combination was defined as bactericidal against all E. coli strains, since minimum bactericidal concentration: minimum inhibitory concentration ratios were below four thresholds and also markedly reduced mutant prevention concentration values of ceftiofur up to 4000-fold compared to its single use. Ceftiofur plus danofloxacin combination inhibited growth of E. coli strains which were resistant to ceftiofur or newer generation of fluoroquinolones. Our results suggest that ceftiofur plus danofloxacin combination has a bactericidal characteristic and can be an important alternative for the treatment of infections caused by resistant E. coli ., Competing Interests: None declared., (© 2022 Urmia University. All rights reserved.)

A prospective, multicentre observational cohort study of carbapenem-resistant Klebsiella spp. (CRK) bloodstream infections was conducted in Turkey from June 2018 to June 2019. One hundred eighty-seven patients were recruited. Single OXA-48-like carbapenemases predominated (75%), followed by OXA-48-like/NDM coproducers (16%). OXA-232 constituted 31% of all OXA-48-like carbapenemases and was mainly carried on ST2096. Thirty-day mortality was 44% overall and 51% for ST2096. In the multivariate cox regression analysis, SOFA score and immunosuppression were significant predictors of 30-day mortality and ST2096 had a non-significant effect. All OXA-48-like producers remained susceptible to ceftazidime-avibactam., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Our knowledge has gaps regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication levels and its association to severity of Coronavirus disease 2019 (COVID-19). The aim of this study was to investigate the association of SARS-CoV-2 viral load with disease severity and serum biomarkers in COVID-19 patients., Methodology: Viral load was determined via cycle threshold (Ct) values of SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 214 adult patients. Ct values were compared with clinical severity, biochemical and hematological biomarkers., Results: Clinical course of the disease was mild (49.1%), moderate (40.2%), and severe (10.7%). Median Ct value was 28.2 (IQR: 22.2-33.8) during the first week of the disease. Ct values were lower within five days after symptom onset [lowest Ct value on the third day (median: 24, IQR: 20.6-32.3)], but they increased significantly during the second and third weeks. No association was detected between admission Ct values and disease severity. Gender, age, co-morbidity, and mortality did not differ significantly in patients with low (≤ 25) and high (> 25) Ct values. White blood cell, neutrophil, platelet, and especially lymphocyte counts, were significantly lower in patients with low Ct values., Conclusions: No definitive/clear correlation between SARS-CoV-2 viral load and severity and mortality was found in the studied COVID-19 patients. However, neutrophil, platelet, and especially lymphocyte count were significantly lower in patients with a high viral load., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Imran Saglik, Beyza Ener, Halis Akalin, Buşra Ozdemir, Gokhan Ocakoglu, Baris Yalcin, Ugur Onal, Ozge Aydin Guçlu, Nilufer Aylin Acet Ozturk, Ulku Tuzemen, Ezgi Demirdogen, Asli Gorek Dilektasli, Harun Agca, Esra Kazak, Funda Coskun, Yasemin Heper, Melda Payaslioglu, Dane Ediger, Ahmet Ursavas, Emel Yilmaz, Cuneyt Ozakin, Esra Uzaslan, Mehmet Karadag.)

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by a devastating decline in cognitive activities among all types of dementia, and it severely affects the quality of life. Late-onset AD (LOAD) occurs after the age of 65 years and develops sporadically. Although aging comes first along the main risk factors underlying LOAD, disease-causing susceptibility genes have been associated with disease pathogenesis. In our study, we included the genes PARP1 , POLB , HTRA2 , SLC1A2 , HS1BP3 , and DRD3 to be investigated in LOAD patients based on their expression levels. Within this framework, we aimed to determine the possible functions of these genes in the pathophysiology of the disease. We investigated whether the utilization of these genes as biomarkers in the early diagnosis of LOAD may help the treatment scheme to be applied in the clinic. We involved 50 individuals in the study and collected peripheral blood samples from the patients and control groups for molecular genetic analysis. Subsequently, RNA was extracted from the peripheral blood samples, and expression analyzes were performed using qualitative reverse transcription polymerase chain reaction. The results obtained were evaluated by using proper statistical methods. Our results demonstrated that there was no difference between patient and control groups in terms of HTRA2 , DRD3 , HS1BP3 , and POLB genes. The expression levels of the SLC1A2 and PARP1 genes were significantly lower in the patient group compared with the control group. In conclusion, we presume that the PARP1 and SLC1A2 genes can be utilized as molecular biomarkers for LOAD., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral immune persistence has been proposed to be affected by patients' characteristics. Moreover, available conflicting assay results are needed to be settled through comparative research with defined clinical specimens. Methods This prospective study investigated SARS-CoV-2-specific antibodies among 43 adults and 34 children at a mean of 12 weeks after the onset of COVID-19 symptoms using six serological assays and compared their performance. We used two Euroimmun (Euroimmun, Luebeck, Germany), two automated Roche Elecsys (Basel, Switzerland), and two rapid immuno-chromatographic Ecotest (Matrix Diagnostics, Assure Tech. (Hangzhou) Co., L, China) assays to investigate SARS-CoV-2 antibodies. Results The findings showed that the Roche Elecsys anti-S total test yielded the best positivity/sensitivity (children 94.1% and adults 93.0%; p = 0.877) while five immunoglobulin IgG targeting assays had similar positivity/sensitivity between children (88.2% to 94.1%) and adults (88.4% to 93.0%) (p > 0.05). Although IgM positivity was relatively low (p < 0.001), it was found in the majority of our pediatric and adult patients (67.6% and 86.0%, respectively; p = 0.098). SARS-CoV-2 S IgG titers were found to be higher among males in pediatric and adult groups compared to females (p = 0.027 and p = 0.041, respectively). Furthermore, we observed significantly higher antibody titers among pneumonia patients (p = 0.001). Conclusion Overall, we concluded SARS-CoV-2 antibody persistence over an average of 12 weeks after the onset of COVID-19 symptoms. While automated Roche Elecsys total antibody assays yielded the best sensitivity (> 90%) and five assays targeting IgG had acceptable performance. Patients with pneumonia and males have higher antibody titers. The effect of antibody persistence on re-infections should be monitored in longitudinal studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Saglik et al.)

Introduction: We aimed to determine the epidemiological change in influenza and other respiratory tract viruses isolated from patients with nasopharyngeal swab samples in our hospital during the COVID-19 period., Methods: We investigated nasopharyngeal swabs for respiratory viruses between March 2020 and February 2021 during the first year of pandemic in Turkey. We used QIAStat Dx Respiratory panel (Qiagen, Germany) in QIAStat Dx (Qiagen, Germany) for detection of respiratory viruses between March 2020 and February 2021. Respiratory panel kit included influenza A, B, influenza A H1N1, rhinovirus/enterovirus, parainfluenza (PIV) 1,2,3,4, coronaviruses (CoVs) NL 63, 229E, OC43 and HKU1, human metapneumovirus (MPV) A/B, bocavirus, respiratory syncytial virus (RSV) A/B and adenovirus., Results: We retrospectively analyzed the results of 319 nasopharyngeal swab samples. The average age of 199 (62.4%) male and 120 (37.6%) female patients between the ages of 0-92 was 16 years. We found that 101 (31.7%) samples were positive for viruses. Rhino/enteroviruses were the most common viruses in all age groups. Influenza positivity rate during the first year of pandemic declined to 2.3% from 17.3% among the previous year. MPV infection activity did not change during the pandemic., Discussion: According to our findings we argue that epidemiology of respiratory viruses has changed during the pandemic period. Despite the current clinical focus on the COVID-19 pandemic, clinicians should keep in mind that rhino/enterovirus and MPV infections may mimic COVID-19 and respiratory infections should be differentially diagnosed with rapid multiplex kits containing SARS-CoV-2, rhino/enterovirus and MPV., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Imatinib mesylate, a tyrosine kinase inhibitor, is the first choice in chronic myeloid leukemia treatment. However, resistance to imatinib may develop with time and in some cases, patients may not respond at all to imatinib. Progressive resistance to imatinib therapy is often due to mutations in the BCR/ABL region. Within the scope of our study 124 patients were evaluated via pyrosequencing between 2015 and 2020. In this regard, 32 patients who have a partial response and have no response to imatinib therapy were included in the study. In addition, next-generation sequencing (NGS) analysis was performed on 15 patients who were resistant to imatinib treatment according to the molecular follow-up reports. With pyrosequencing, 5 cases out of a total of 124 were found to be positive. This means that approximately 4.03% of the proportion is positive. But when we examined only 32 patients who have a partial response and have no response to imatinib therapy this rate is rising 15.6%. NGS analysis was performed with 15 patients who have no mutation with pyrosequencing of 32 patients and VUS (Variant of Uncertain Significance) mutation was detected in one. In this study, our aim was to determine the mutations of the BCR/ABL and to evaluate the mutations by NGS and pyrosequencing. Our study is important in terms of comparing the pyrosequencing with NGS mutation rates, drawing attention to the clinical importance of log reduction., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Vancomycin-resistant enterococcus (VRE) is an infectious agent that can increase morbidity and mortality, especially in patients with neutropenia in haematology departments. We analysed VRE infections and mortality rates among VRE colonized patients with acute leukaemia, defined predisposing risk factors for infection and mortality, and investigated the influence of daptomycin or linezolid treatment on mortality., Patients-Methods: We included 200 VRE colonized adult acute leukaemia patients with febrile neutropenia between January 2010 and January 2016. Data were collected from electronic files., Results: There were 179 patients in the colonized group, and 21 patients in the infected group. Enterococcus faecium (van A) was isolated from all patients. The infection rate was 10.5 %, and the types of infections noted were as follows: bloodstream (n = 14; 66.7 %), skin and soft tissue (n = 3; 14.3 %), urinary (n = 2; 9.5 %), and others (9.5 %). In the multivariate logistic regression analysis, exposure to invasive procedures, coinfection status, and >15 days of VRE positivity were independent risk factors for VRE infections. In hospital mortality rates were 57.1 % in the infected group, and 9.5 % in the colonized group (p < 0.001). Older age, female gender, absolute neutropenia, and coinfection status were statistically significant predictor of survival., Conclusion: Vancomycin-resistant enterococcus infections are associated with high morbidity and mortality in haematology patients with neutropenia. Clinicians should be aware of predisposing risk factors for VRE infection to avoid unfavourable outcomes. We believe that larger studies are necessary regarding the influence of treatment with daptomycin and linezolid., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The secretion of interleukin (IL)-1 family cytokines is one of the most potent and earliest pro-inflammatory responses triggered by brucellosis. However, the roles of the most recently discovered IL-1 family members, IL-36, IL-37, and IL-38, in the transition into the chronic form of brucellos is remain largely unknown. Therefore, in this study, the roles of IL-36, IL-37, and IL-38 in brucella infections and their effects on the transition from the acute to chronic form of the disease were investigated. Using peripheral blood samples from 40 patients with acute brucellosis, 40 patients with chronic brucellosis, and 40 healthy control subjects, we analysed the serum concentrations of secreted IL-36, IL-37, and IL-38 using ELISA. The findings were confirmed by using RT-qPCR to analyse the mRNA levels of the genes encoding IL-36, IL-37, and IL-38 in peripheral blood mononuclear cells (PBMCs) from 10 randomly selected patients from each of the three groups. Our results showed that serum IL-37 (p < 0.001) and IL-38 (p < 0.001) concentrations were lower in patients with brucellosis than in the healthy controls. In addition, serum IL-37 and IL-38 concentrations were higher in the chronic patient group than in the acute patient group. The mRNA expression levels of IL-37 and IL1F10, genes that encode IL-38, did not affect serum cytokine secretion levels. This result suggests that the high secretion levels of IL-37 and IL-38 may be related to the progression into the chronic form of brucellosis. Our findings will aid in clarifying the mechanism of the transition of brucellosis from the acute to the chronic form of the disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: This study was done to determine the changes in expression levels of PERIOD family genes in chronic insomnia patients and night shift healthcare staff with irregular sleep hours., Method: A total of 24 chronic insomnia patients aged between 25 and 55 that were admitted to Erciyes University Medical Faculty Neurology Polyclinic, 32 medical staff aged between 23 and 42 that work in night shifts with no neurological diagnosis were included as volunteers in the experiment. Additionally, a control group consisting of 29 healthy individuals between 21 and 50 years of age who do not work in shifts was volunteered in the study. Since PERIOD family gene expressions are affected by time of day and season changes, blood samples were taken from the groups within the same week and at the same time periods. RNA isolation followed by cDNA synthesis from leukocytes was performed from blood samples that were kept in 10 cc EDTA tubes. Expression levels of the genes were then determined by quantitative PCR method and analysed., Results: There was a significant decrease in the expression levels of PER1 and PER2 genes in chronic insomnia and night shift healthcare professional groups compared to the control group (p = 0.0001 for PER1; p = 0.0023 for PER2), but no significant change was observed in PER3 gene (p = 0.619)., Discussion: The decrease in PER1 and PER2 gene expressions in chronic insomnia and shift working healthcare personnel seems to be more of a result for short sleep periods than a cause., (Copyright © 2020. Published by Elsevier B.V.)

Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder due to presence of mutations in the genes involved in the metabolism of steroid hormones in adrenal gland. There are two main forms of CAH, classic form and non-classic form. While classic form stands for the severe form, the non-classic form stands for the moderate and more frequent form of CAH. The enzyme deficiencies such as 21-hydroxylase, 11-beta-hydroxylase, 3-beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase deficiencies are associated with CAH. In this study, we aimed to investigate CYP21A2, CYP11B1, HSD3B2 genes which are associated with 21-hydroxylase, 11-beta-hydroxylase and 3-beta-hydroxysteroid dehydrogenase enzyme deficiencies, respectively, in 365 individuals by using Sanger sequencing method. We emphasized the classification of variants according their disease causing potential, and evaluated variants' frequencies including newly discovered novel variants. As a result, 32 variants of CYP21A2 including 10 novel variants, 9 variants of CYP11B1 including 3 novel variants and 6 variants of HSD3B2 including 4 novel variants were identified. The conclusions of our study showed that in Anatolia, discovery of novel variants is quite common on account of tremendous ratios of consanguineous marriages which increases the frequency of CAH. These results will contribute to the understanding of molecular pathology of the disease.

Objective: In this study, we investigated the frequency of Epidermal growth factor receptor (EGFR) gene mutations, the level of EGFR mRNA and protein expressions in Turkish population for indicating substantial differences in the frequency of EGFR mutations, EGFR amplification and EGFR protein expression between populations and the effect of these parameters in response to EGFR tyrosine kinase inhibitors., Materials and Methods: The study included 34 patients with non-small cell lung cancers. The RNA and DNA were extracted from the normal and tumor side of the lung tissue removed by surgery. To investigate the most common mutations in the EGFR gene, exon 19 was sequenced and mutation specific PCR was performed for detecting the L858R mutation in exon 21. EGFR mRNA expression was measured by relative quantitative reverse transcription PCR. The EGFR protein levels were detected with immunohistochemistry methods from the sections of the patients' paraffin blocks., Results: No EGFR mutation in exon 19 or L858R mutation in exon 21 were detected in the patients. Overexpression of EGFR gene mRNA was identified in 16 of 34 (%47) patients and overexpression of EGFR protein was detected in 15 of 34 (%44) patients. Statistical analysis was not significant for the correlation between sex, age, smoking, histopathology, pathological stage and overexpression of EGFR mRNA and protein., Conclusion: It was found that in Turkish population, EGFR mutation in exon 19 and L858R mutation were very rare, EGFR protein expression was similar and EGFR mRNA expression significantly increased compared to the literature. Markedly increased EGFR mRNA expression ratios in the absence of activating mutations showed that identifying the EGFR mRNA expression level for prediction of response to EGFR tyrosine kinase inhibitors might be significant in the Turkish population., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare.

BACKGROUND Ventilator-associated pneumonia (VAP) is a nosocomial infection commonly seen in patients in intensive care units (ICU). This study aimed to analyze factors affecting prognosis of patients diagnosed with VAP. MATERIAL AND METHODS Critically ill patients with VAP were retrospectively evaluated between June 2002 and June 2011 in the ICU. VAP diagnosis was made according to 2005 ATS/IDSA (Infectious Diseases Society of America/American Thoracic Society) criteria. First pneumonia attacks of patients were analyzed. RESULTS When early- and late-onset pneumonia causes were compared according to ICU and hospital admittance, resistant bacteria were found to be more common in pneumonias classified as early-onset according to ICU admittance. APACHE II score of >21 (p=0.016), SOFA score of >6 (p<0.001) on admission to ICU and SOFA score of >6 (p<0.001) on day of diagnosis are risk factors affecting mortality. Additionally, low PaO2/FIO2 ratio at onset of VAP had a negative effect on prognosis (p<0.001). SOFA score of >6 on the day of VAP diagnosis was an independent risk factor for mortality [(p<0.001; OR (95%CI): 1.4 (1.2-1.6)]. CONCLUSIONS Resistant bacteria might be present in early-onset VAP. Especially, taking LOS into consideration may better estimate the presence of resistant bacteria. Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA) were the most frequent causative microorganisms for VAP. SOFA score might be more valuable than APACHE II score. Frequently surveilling SOFA scores may improve predictive performance over time.

Background: In many cases of suspected sepsis, causative microorganisms cannot be isolated. Multiplex real-time PCR generates results more rapidly than conventional blood culture systems., Methods: In this study, we evaluated the diagnostic performance of multiplex real-time PCR (LightCycler® SeptiFast, Roche, Mannheim, Germany), and compared with blood cultures and cultures from focus of infection in nosocomial sepsis., Results: Seventy-eight nosocomial sepsis episodes in 67 adult patients were included in this study. The rates of microorganism detection by blood culture and PCR were 34.2% and 47.9%, respectively. Sixty-five microorganisms were detected by both methods from 78 sepsis episodes. Nineteen of these microorganisms were detected by both blood culture and PCR analysis from the same sepsis episode. There was statistically moderate concordance between the two methods (κ=0.445, P<0.001). There was no significant agreement between the blood culture and PCR analysis in terms of microorganism detected (κ=0.160, P=0.07). Comparison of the results of PCR and cultures from focus of infection revealed no significant agreement (κ=0.110, P=0.176). However, comparison of the results of PCR and blood cultures plus cultures from focus of infection (positive blood culture and/or positive culture from focus of infection) showed poor agreement (κ=0.17, P=0.026). When the blood culture was used as the gold standard, the sensitivity, specificity, positive and negative predictive value of PCR in patients with bacteremia was 80%, 69%, 57% and 87%, respectively., Conclusions: SeptiFast may be useful when added to blood culture in the diagnosis and management of sepsis.

Background/aim: Invasive aspergillosis (IA) is a fatal infection that is difficult to diagnose in immunocompromised patients. In this study, Aspergillus-specific DNA was searched using real-time PCR (RT-PCR) in serum samples. Galactomannan (GM) and/or beta-D-glucan (BDG) tests were previously performed on these samples for 70 neutropenic patients with hematological malignancy., Materials and Methods: The patients were categorized according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG). Among the patient serum samples, the first positive GM or BDG test sample and the median sample of GM or BDG test for negative patients were used to detect DNA levels by RT-PCR method (Light Cycler 480, Roche Molecular Biochemicals, Meylan, France) using a commercial kit (Way2Gene Fungi; Genmar, İzmir, Turkey)., Results: When the proven and probable IA group were considered as real patients, sensitivity of Aspergillus-specific DNA test was 90%, specificity was 73.3%, positive predictive value was 81.8%, and negative predictive value was 84.6%., Conclusion: This study found that searching for specific DNA by RT-PCR method has a sensitivity as high as the GM test. Although specificity was rather low, it was concluded that it can be used jointly with GM and BDG tests after decreasing contamination by severe laboratory applications.

Background/aims: In this study, the sensitivity-specificity of galactomannan-enzyme immunoassay (GM-EIA) with a cut-off value of 0.5 for a single, two, or three consecutive positivity in the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients with hematological malignancy was investigated., Methods: IPA was classified as "proven," "probable," or "possible" as described in the guidelines prepared by the European Organization for Research and Treatment of Cancer and Mycoses Study Group." Serum samples were collected from the patients twice a week throughout their hospitalization. A total of 1,385 serum samples, with an average of 8.3 samples per episode, were examined., Results: Based on the 165 febrile episodes in 106 patients, 80 (48.5%) were classified as IPA (4 proven, 11 probable, 65 possible) and 85 (51.5%) as non-IPA. The sensitivity/ specificity was 100%/27.1% for a single proven/probable IPA with the cut of value of GM-EIA ≥ 0.5, 86.7%/71.8% for two consecutive positive results, and 73.3%/85.9% for three consecutive positive results., Conclusions: With the galactomannan levels measured twice a week, consecutive sensitivity decreased and specificity increased. Therefore, an increase may be obtained in sensitivity-specificity by more frequent monitoring of GM-EIA starting from the first day of positivity is detected.

Background: Invasive fungal infections are a major cause of morbidity and mortality among renal transplant recipients., Objectives: The aim of this study was to investigate the frequency and risk factors for fungal infections in renal transplant recipients., Methods: We retrospectively evaluated all kidney transplant recipients at our center from December 1988 to June 2010 for the epidemiology, spectrum, risk factors, and mortality of invasive fungal infections., Results: In 32 patients (10.30 %), at least one fungal infection developed after the transplantation. The most common pathogens causing fungal infections in our patients were Candida spp. and Aspergillus spp. The independent risk factors associated with invasive fungal infection episodes were antibiotic treatment within the last 3 months (OR 15.88, 95 % CI 3.90-64.73, p < 0.001), cytomegalovirus infection (OR 18.54, 95 % CI 9.01-38.17, p < 0.001), and the presence of diabetes mellitus (OR 6.01, 95 % CI 2.95-12.25, p < 0.001). Mortality was significantly higher among patients with fungal infections than among other patients (53.10 and 17.80 %, respectively; p < 0.001)., Conclusions: It is difficult to diagnose and treat fungal infections early, and it can be useful to determine independent risk factors in order to identify and treat high-risk patients.

The roles of CRP, PCT, serum amyloid A (SAA), and cytokines in the diagnosis of fungal infections have not yet been clearly demonstrated. This study aims to measure the serum levels of interleukin (IL)-23, IL-17, IL-1β, tumor necrosis factor (TNF)-α, IL-10, transforming growth factor (TGF)-β, C-reactive protein (CRP), procalcitonin (PCT), and serum amyloid A (SAA) in cases of candidemia and to compare them with those observed in cases of bacteremia. For this purpose, the serum cytokine levels from 50 patients with candidemia were compared with those of 14 patients with polymicrobial sepsis, 30 patients with bacteremia, and 27 healthy control subjects. The cytokine levels were studied using sandwich ELISAs according to the manufacturer protocol. The serum levels of TGF-β, IL-23, and IL-17 were found to be significantly higher in the candidemia group in comparison with the samples from those with bacteremia and healthy controls. The PCT and SAA levels were higher in samples from the group with bacteremia those from individuals with candidemia and the healthy control group. Assuming an IL-17 level threshold of >38.79 pg/ml, the sensitivity and specificity were 38% and 96.6%, respectively but considering an IL-23 threshold of >59.97 pg/ml, the sensitivity and specificity values were found to be 72% and 60%, respectively. The sensitivity and the specificity of the TGF-ß levels were found to be 85.71% and 53.33%, respectively, when the TGF-ß threshold is >560 pg/ml. PCT and SAA demonstrated a superior performance for the differentiation of candidemia and bacteremia. Our study demonstrates that IL-17, IL-23, TGF-ß, PCT, and SAA levels could be a diagnostic marker for candidemia., (© The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Despite the clinical importance of the leukemic transformation of chronic myeloproliferative neoplasms (MPNs), very little is known about markers that predict leukemic transformation. We studied WT1 expression in 37 MPN patients diagnosed as bcr-abl negative and JAK2 (V617F) positive with a molecular genetic test, and 23 healthy controls., Results: WT1 expression is higher in MPN patients compared with normal controls (p=0.002). According to the WT1 expression levels, patients were divided into two groups: high (≥0.205) and low (0-0.205) WT1 expression. Two out of six patients with a high WT1 expression level transformed to myelodysplastic syndrome at a 42- and 46-month follow-up, respectively., Conclusions: Our results suggest that the overexpression of WT1 may play an important role in the leukemic transformation of MPNs.

Introduction: Ghrelin is a hormone which has effects on the secretion of growth hormone, gastrointestinal system, cardiovascular system, cell proliferation and reproductive system. The present study we focused on the relation between ghrelin and GHS-R1a gene expression and the regulation of their expression in the testes of diabetic rats., Material and Methods: 40 male Wistar albino rats were divided into four groups: control, and sampled 4, 8 and 12 weeks after induction of diabetes by streptozotocin (STZ) intraperitoneal injection (40 mg/kg). The rats were decapitated under ketamine anesthesia and their testes were removed. Blood was obtained from heart and serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were measured by ELISA. Tissue ghrelin and GHS-R mRNA levels were determined by qRT-PCR, while ghrelin protein expression was studied by immunohistochemistry. Histopathological damage scores were also assessed., Results: Eight weeks after diabetes induction serum FSH level was increased, whereas LH and testosterone concentrations decreased. The ghrelin and GHS-R1a gene expression and ghrelin immunohistochemistry score first tended to increase after first four weeks of diabetes, and then tended to decrease. Ghrelin-immunopositive cells were detected in Leydig cells in all groups of rats, however, not in the germinal epithelium. Congestion of vessels and hemorrhage, formation of the vacuoles in spermatogonia and spermatocytes, desquamation of spermatids in the lumen and disorganization of seminiferous tubule germinal epithelium were observed in testis of all the diabetic rats. In addition, mean testicular biopsy score and mean seminiferous tubule diameter were getting lower in diabetic animals., Conclusion: Our results suggest that diabetes affects ghrelin expression in rat testis.

Introduction: Routes of transmission and reasons for HIV testing are important epidemiologic data to analyze the epidemic and to tailor the response to AIDS. The aim of this study was to analyze reasons for testing and transmission ways of HIV among recently diagnosed HIV patients registered in the multicenter HIV-TR cohort in Turkey., Methods: Transmission ways and reasons for testing of all patients diagnosed in 2011 and 2012 were recorded on a web-based data collection system and were analyzed retrospectively., Results: The study included 693 patients (561 male, 132 female) from 24 sites. Reason for HIV testing was available in 640 patients (92%). The most common reason for HIV testing was diagnostic workout for other conditions or illness followed by patient-initiated testing. The reasons for testing were listed in Table 1. The most common routes of HIV transmission were heterosexual intercourse (62.7%) and sex among men who have sex with men (MSM) (22.6%). At the time of HIV diagnosis, the mean CD4 lymphocyte cell count was 355/mm(3) (3-1433/mm(3)). Primary HIV infection was determined in 42/693 (6%) patients and 9/693 (% 1, 2) cases were considered "probable primary HIV infection." The majority of the cases presented to a clinic for follow-up right after the diagnosis. On the other hand 32/616 (5.2%) patients delayed their presentation for more than 3 months. The longest delay was 11 months., Conclusions: The results of the database suggest that targeted testing is lacking in the country. The shift toward homosexual transmission during the last 2 years emphasizes the need for targeted interventions. Patients present relatively late and HIV infection could only be diagnosed when immunosuppression related findings appeared. Patient-initiated testing,an indicator of awareness, was very low suggesting a need to scale-up awareness raising interventions.

Introduction: HIV-TR is a recently established (2012) multicentre cohort in Turkey. The aim of this study is to analyze epidemiological, immunologic and virologic data of recently diagnosed HIV patients., Materials and Methods: Epidemiologic, clinical and laboratory data of all patients diagnosed in 2011 and 2012 were recorded by a web-based data collection system, retrospectively., Results: A total of 693 patients (561 male, 132 female) at 24 sites were enrolled. The median age at first presentation for HIV care was 36. The proportion of patients presenting with advanced HIV disease (CD4 count<200/mm(3) or presenting with an AIDS-defining event) was 30.6%; and 52.4% of patients were late presenters (CD4 count<350/mm(3) or presenting with an AIDS-defining event). Median CD4 counts at presentation and before treatment were 344 (IQR: 175-540) and 295 (IQR: 150-430), respectively. Pretreatment CD4 count was >500 copies/mL in 18.5% of patients. Of 531 patients receiving ART, initial combinations consist of tenofovir/emtricitabine (TDF/FTC) plus efavirenz (EFV) in 48.2% and TDF/FTC plus lopinavir/ritonavir (LPV/r) in 37.5% and other combinations in 14.3% of the patients. Pre-treatment HIV-RNA was over 100.000 copies/mL in 52.3% of patients. At Weeks 24 and 48, HIV-RNA were<50 copies/mL in 63,4% of 385 patients and 82% of 311 patients reported to be still on ART and had a viral load measurement, respectively. Median pretreatment CD4 count was lower for TDF/FTC+LPV/r recipients than TDF/FTC+EFV recipients (250 vs 316) (p<0.05). The median increase from baseline CD4 cell count was 230 in TDF/FTC+LPV/r group, 193 in TDF/FTC+EFV group and 216 among all treated patients. Of 531 patients receiving ART, 11 had died and 19 were lost to follow-up., Conclusion: Despite 52.4% of recently diagnosed patients were late presenters; a high rate of virologic suppression was achieved in HIV-TR Cohort. A national HIV testing strategy targeting subpopulations with higher risk is urgently needed.

Objectives: Pneumonia is an important cause of morbidity and mortality in recipients of solid-organ transplant. We aimed to determine risk factors for development of pneumonia and associated deaths in kidney transplant recipients., Materials and Methods: A retrospective review of medical records was performed for all kidney transplant recipients from December 1988, to April 2011. The diagnosis of community-acquired pneumonia was made from symptoms, clinical findings, and chest radiography. The diagnosis of nosocomial pneumonia was made according to published criteria. Laboratory and serologic tests, radiographic findings, cultures of respiratory specimens, and tissue biopsies were reviewed., Results: In 406 kidney transplant recipients, there were 82 patients (20%) who had 111 episodes of pneumonia, including 49 nosocomial episodes of pneumonia (44%). Bacterial infections were the most common cause (34 episodes [31%]). In multivariate analysis, significant risk factors associated with pneumonia episodes were older age, hypertension, cardiac disease, history of acute graft rejection, and not using everolimus/mycophenolate mofetil/prednisolone protocol. There were 28 episodes that resulted in death (25%), including 20 nosocomial episodes (71%). In multivariate analysis, significant risk factors associated with death from pneumonia episodes were antibiotic use in the previous 3 months, high C-reactive protein, and low albumin. Cutoff values for increased risk of death from pneumonia included C-reactive protein > 10 mg/dL and procalcitonin > 8.8 ng/mL., Conclusions: Recipients of kidney transplant may be at risk for pneumonia and associated death. Nosocomial pulmonary infections may be associated with marked morbidity and mortality in kidney transplant recipients.

Background: The aim of this study was to determine the distribution of vancomycin and daptomycin MICs among methicillin-resistant Staphylococcus aureus (MRSA) blood isolates, the prevalence of heterogeneous vancomycin-intermediate S. aureus (hVISA) and the relationship between hVISA and vancomycin MIC values., Methods: A total of 175 MRSA blood isolates were collected from seven university hospitals in Turkey. All isolates were tested for susceptibility to vancomycin and daptomycin by reference broth microdilution (BMD) and by standard Etest method. BMD test was performed according to CLSI guidelines and Etest was performed according to the instructions of the manufacturer. All isolates were screened for the presence of the hVISA by using macro Etest (MET) and population analysis profile-area under the curve (PAP-AUC) methods., Results: The vancomycin MIC50, MIC90 and MIC ranges were 1, 2, and 0.5-2 μg/ml, respectively, by both of BMD and Etest. The daptomycin MIC50, MIC90 and MIC ranges were 0.5, 1 and 0.125 -1 μg/ml by BMD and 0.25, 0.5 and 0.06-1 μg/ml by Etest, respectively. The vancomycin MIC for 40.6% (71/175) of the MRSA isolates tested was >1 μg/ml by BMD. No vancomycin and daptomycin resistance was found among MRSA isolates. Percent agreement of Etest MICs with BMD MICs within ±1 doubling dilution was 100% and 73.1% for vancomycin and daptomycin, respectively. The prevalence of hVISA among MRSA blood isolates was 13.7% (24/175) by PAP-AUC method. MET identified only 14 of the hVISA strains (sensitivity, 58.3%), and there were 12 strains identified as hVISA that were not subsequently confirmed by PAP-AUC (specificity, 92.1%)., Conclusions: Agreement between BMD and Etest MICs is high both for vancomycin and daptomycin. Daptomycin was found to be highly active against MRSA isolates including hVISA. A considerable number of isolates are determined as hVISA among blood isolates. As it is impractical to use the reference method (PAP-AUC) for large numbers of isolates, laboratory methods for rapid and accurate identification of hVISA need to be developed.

Background: In the past, Staphylococcus aureus infections have displayed various patterns of epidemiologic curves in hospitals, particularly in intensive care units (ICUs). This study aimed to characterize the current trend in a nationwide survey of ICUs in Turkey., Methods: A total of 88 ICUs from 36 Turkish tertiary hospitals were included in this retrospective study, which was performed during the first 3 months of both 2008 (period [P] 1) and 2011 (P2). A P value ≤.01 was considered significant., Results: Although overall rates of hospital-acquired infection (HAI) and device-associated infection densities were similar in P1 and P2, the densities of HAIs due to S aureus and methicillin-resistant S aureus (MRSA) were significantly lower in P2 (P < .0001). However, the proportion of HAIs due to Acinetobacter was significantly higher in P2 (P < .0001)., Conclusions: The incidence of S aureus infections is declining rapidly in Turkish ICUs, with potential impacts on empirical treatment strategies in these ICUs., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Diagnosing GABHS (Group A-beta Hemolytic Streptococcus) tonsillopharyngitis by clinical scoring is a recommended approach in developed countries, but there is still much controversy for low resource settings., Aim: We aimed to assess the impact of Centor criteria with the support of practical laboratory tests., Methods: We prospectively included patients complaining sore throat (N = 282). We evaluated them in terms of Centor scoring and performed white blood cell count (WBC), C-reactive protein (CRP), rapid antigen detecting test, and throat culture., Results: In GABHS cases (N = 32, 11·3%), two of the criteria were observed to be positive in more than half of the cases (N = 19, 59·3%), while 13 (40·7%) cases met three/four criteria. The specificity of having two criteria was found to be 65·5% and increased to 91·5% after including CRP and WBC., Conclusion: Centor criteria could be safely used to reduce unnecessary antibiotic usage for tonsillopharyngitis in developing countries.

The incidence of invasive aspergillosis has increased after solid organ transplant. However, aspergillus osteomyelitis in vertebrae is rare. We report a case of aspergillus spondylodiskitis after pulmonary aspergillosis in a renal transplant recipient. He was treated by antifungal therapy and surgical intervention. The transplantist should be alert for a diagnosis of aspergillus spondylodiskitis in recipients who developed back pain after aspergillosis infection in other sites.

Partial Trisomy 14q is a rare chromosomal disorder that mostly results from a parental translocation. We report here a newborn boy with partial trisomy 14q and dysmorphic features that are compatible with previously reported cases. Conventional cytogenetic analysis revealed an extra chromosomal segment at the end of the short arm of chromosome 4. In order to determine the origin of this chromosome region we used subtelomeric FISH technique. Based on the results of these cytogenetic studies and the physical examination, this dysmorphic case was diagnosed as partial trisomy of 14q and his karyotype determined as 46 XY, der(4)t(4;14)(p16;q32) resulting from a balanced maternal translocation identified as 46,XX, t(4;14)(p16;q32).