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Objectives: Posttransplant lymphoproliferative disorder is a consequential complication following solid-organ transplant, particularly associated with the Epstein-Barr virus. We studied a single center's cases of pediatric posttransplant lymphoproliferative disorder for a 7-year period and focused on incidence rates, anatomic sites involved, and correlation with clinical outcomes. We explored clinical features and treatment outcomes in patients with pediatric posttransplant lymphoproliferative disorder, with emphasis on patient survival and associated clinical ramifications., Materials and Methods: This was a retrospective analysis of medical records from pediatric solid-organ transplant recipients (liver or kidney) at Baskent University Ankara Hospital Organ Transplantation Center between January 1, 2017, and January 1, 2024, approved by the Institutional Review Board (KA24/63). We identified cases based on pathology-confirmed persistent lymphadenopathy or tumorous lesions. Patient categorization distinguished between malignant and benign groups. Early posttransplant lymphoproliferative disorder was defined within the initial year after transplant. Epstein?Barr virus association was determined through in situ hybridization, and patient characteristics were reviewed comprehensively., Results: In 7 years, 10 pediatric patients (9 liver transplants, 1 kidney transplant) were diagnosed with posttransplant lymphoproliferative disorder, with an incidence of 8.7% for pediatric liver transplants. Mean age at diagnosis was 46.4 months, and mean time from transplant to diagnosis was 21.2 months. The most common complaints at diagnosis included fever, lymphadenopathy, hepatosplenomegaly, dyspnea, and diarrhea. Treatment modalities included rituximab, immunosuppression reduction, intravenous immunoglobulin therapy, and chemotherapy (NHL Berlin-Frankfurt-Münster 90 protocols). All patients achieved remission (mean follow-up, 22.9 mo)., Conclusions: Early diagnosis of posttransplant lymphoproliferative disorder is important, and rituximab with immunosuppression reduction is effective to achieve complete remission, particularly in early polymorphic cases. Despite challenges, all patients achieved remission, signaling improved outcomes in pediatric posttransplant lymphoproliferative disorder. Active monitoring of Epstein?Barr virus infection may further reduce posttransplant lymphoproliferative disorder complications in pediatric solid-organ transplant; hence, early diagnosis is crucial.

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of neurodegenerative disorders characterized by hypoplasia and degeneration of the cerebellum and pons. We aimed to identify the clinical, laboratory, and imaging findings of the patients with diagnosed PCH with confirmed genetic analysis. We collected available clinical data, laboratory, and imaging findings in our retrospective multicenter national study of 64 patients with PCH in Turkey. The genetic analysis included the whole-exome sequencing (WES), targeted next-generation sequencing (NGS), or single gene analysis. Sixty-four patients with PCH were 28 female (43.8%) and 36 (56.3%) male. The patients revealed homozygous mutation in 89.1%, consanguinity in 79.7%, pregnancy at term in 85.2%, microcephaly in 91.3%, psychomotor retardation in 98.4%, abnormal neurological findings in 100%, seizure in 63.8%, normal biochemistry and metabolic investigations in 92.2%, and dysmorphic findings in 51.2%. The missense mutation was found to be the most common variant type in all patients with PCH. It was detected as CLP1 (n = 17) was the most common PCH related gene. The homozygous missense variant c.419G > A (p.Arg140His) was identified in all patients with CLP1. Moreover, all patients showed the same homozygous missense variant c.919G > T (p.A307S) in TSEN54 group (n = 6). In Turkey, CLP1 was identified as the most common causative gene with the identical variant c.419G > A; p.Arg140His. The current study supports that genotype data on PCH leads to phenotypic variability over a wide phenotypic spectrum., (© 2024. The Author(s).)

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear., Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis., Results: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability (GDD/ID), infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe GDD/ID, absent speech, and autistic features, while seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, in particular in pre-rRNA processing., Conclusion: This study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of 'ribosomopathies'., (Copyright © 2024. Published by Elsevier Inc.)

Background: Coronavirus disease 2019 (COVID-19) is a multisystem disease of global significance. Interleukin (IL)-6 is a soluble cytokine with a pleiotropic effect on inflammation and the immune response., Objectives: Investigate the relationship between the interleukin 6 (IL6 ) rs1800795 variant and IL6 level in Turkish patients with COVID-19 disease., Design: Prospective cohort study., Setting: Tertiary care hospital., Patients and Methods: Real-time polymerase chain reaction (RT-PCR)-positive and/or chest computerized tomography ( CT) scan - compatible COVID-19 patients were enrolled in the study. The clinical data and whole blood samples were collected from April 1, 2020, to August 1, 2020. IL6 rs1800795 genotyping was performed by the PCR-restriction fragment-length polymorphism (RFLP) method in 148 patients. Serum IL-6 concentrations were measured using the ELISA method in 89 patients. We evaluated the patients in three groups: asymptomatic, symptomatic, and intensive care unit patients., Main Outcome Measures: IL6 rs1800795 genotype frequencies and serum IL-6 levels in COVID-19 patients with different clinical presentations., Sample Size: 148 cases., Results: IL6 rs180079 5 GG genotype and G allele frequency increased in PCR positive patients compared to PCR-negative patients ( p ˂ 0.000). IL6 rs1800795 GC genotype and C allele frequency were lower in PCR-positive patients than in PCR-negative patients. IL6 rs1800795 GG genotype and G allele frequency were higher in asymptomatic patients than in the symptomatic and intensive care unit groups. The IL6 rs1800795 C allele frequency was lower in asymptomatic patients than in the symptomatic and intensive care unit groups. IL6 rs1800795 GG genotype and G allele frequency were higher in CT negative patients than CT positive patients, while IL6 GC genotype and C allele frequency were higher in CT positive patients than negative patients. IL6 level elevation was seen in the asymptomatic patients compared to the symptomatic and intensive care unit groups., Conclusions: These findings suggest that IL6 rs1800795 may contribute to the susceptibility of COVID-19 in people to Turkish origin., Limitations: Further large-scale studies in different genetic populations are needed as this is a single-center, prospective study.

Low vitamin D levels and adverse effects have been reported in SARS-COV-2 positive patients. This study examined the effect of the vitamin D receptor gene BsmI polymorphism on SARS-COV-2 positive patients. A total of 80 SARS-COV-2 positive inpatients were included in the study, and 110 healthy individuals were included as a control group. The 25-(OH) vitamin D3, lymphocyte, and activated partial thromboplastin time levels of SARS-COV-2 positive patients were lower than those of the control group. The prothrombin time (PT), international normalized ratio (INR), D-dimer, C-reactive protein (CRP), procalcitonin, and ferritin levels of SARS-COV-2 positive patients were higher than those of the control group. A negative correlation was found between 25-(OH) vitamin D3 levels and white blood cell count, PT, INR, D-dimer, CRP, procalcitonin, and ferritin levels in SARS-COV-2 positive patients. The 25-(OH) vitamin D3 level in individuals with the BB genotype was higher than the 25-(OH) vitamin D3 level in individuals with the Bb and bb genotype. A statistically significant difference was found between the groups in terms of the genotype and allele distributions of BsmI polymorphism. When the genotypes were analyzed in terms of bb versus Bb + BB, a statistically significant difference was found between the groups. However, this finding was not found between the intensive care inpatient subgroup and the other inpatient subgroup. In conclusion, BsmI b allele and bb genotype were associated with hospitalization for SARS-COV-2 infection. This may be because individuals with b allele have low levels of vitamin D.

The most important complication of familial Mediterranean fever (FMF) is secondary amyloidosis. The aim of this study is to investigate the risk of developing FMF-related amyloidosis with macrophage migration inhibitory factor (MIF), interleukin 4 (IL-4), and IL-1 receptor antagonist (IL-1RA) variants. This study included 62 FMF patients with amyloidosis, 110 FMF patients without amyloidosis, and 120 controls. The clinical information of the patient groups was compared. MIF-173G/C , IL-4 variant number tandem repeat (VNTR), and IL-1RA VNTR variants were analyzed for all participants. The use of colchicine, pleurisy, and appendectomy was more common in FMF patients with amyloidosis than in FMF patients without amyloidosis. MIF-173G/C C/C genotype and C allele were higher in both patient groups compared to controls. IL-1RA VNTR A1/A2 and A1/A4 genotypes and A1-A4 alleles were more common in both patient groups than controls. The IL-4 VNTR P1 allele was more common in FMF patients with amyloidosis compared to controls. The MIF-173G/C allele and the IL-1RA VNTR A1-A4 allele are associated with FMF in the Turkish population but not with amyloidosis risk in FMF patients. The IL-4 VNTR P1 allele is more common in FMF patients with amyloidosis than in healthy individuals., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Flattery is one of the oldest and most commonly used impression-management tactics in everyday life. Though it often brings benefits to the flatterer, less is known about how it affects the target. In the present research, we explore when and why being flattered can be costly for leaders-common targets of flattery-depending on how they respond to it. We suggest that leaders who are observed rewarding flatterers risk appearing naïve to others. Across seven studies and six supplementary studies ( N = 4,612), we find evidence that leaders who grant favors to flatterers are often perceived to have naively "fallen for flattery," which shapes observers' impressions of the leaders and the organizations they represent. A first set of studies (Studies 1-4) detail the variety of factors that lead observers to conclude their leader has fallen for flattery and the resulting impacts to the leaders' reputation and their organization (e.g., competence, warmth, commitment to the leader, organizational fairness). The second set of studies look at the contextual factors that impact what costs leaders pay for being perceived to have fallen for flattery, including the type of flattery (Study 5), who is harmed by the favor (Study 6), and the leader's apparent awareness of the motives underlying flattery (Study 7). Whereas previous research highlights positive consequences of flattery for the flatterer, we find that flattery comes with costs for leaders and their organizations. We discuss theoretical and practical implications for leaders who are frequently flattered. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Research Question: What are the embryonic profiles and oocyte maturation dynamics in patients with tubulin beta eight class VIII (TUBB8) mutations leading to oocyte maturation abnormalities (OMAS), and are pregnancies possible in this population?, Design: A prospective cohort study was undertaken in a private fertility clinic between January 2019 and December 2022. Whole-exome genomic studies (WES) were performed to detect mutation types. In-vitro maturation (IVM) was compared in 18 subjects: nine with TUBB8 mutations, and nine without TUBB8 mutations to act as the control group. The distributions of oocyte maturation and embryonic development profiles were recorded. IVF and IVM outcomes of the 18 cases were evaluated. The primary outcomes were the embryonic profiles and maturation dynamics of oocytes derived from IVF or IVM in women as related to TUBB8 mutations., Results: Mutations were detected in 52 of 89 (58.4%) women who underwent WES analysis. Twelve TUBB8 mutations were detected in nine women (10.1%) with OMAS. Seven novel TUBB8 mutations were noted. Two pregnancies were obtained in women with c.535 G>A TUBB8 mutations. When comparing IVM outcomes between women with and without TUBB8 mutations, there were no differences in oocyte, embryo or pregnancy parameters (P>0.05 in all cases)., Conclusions: It is clear that further TUBB8 mutations which cause oocyte or embryonic arrest will be detected in future. Although biochemical or ectopic pregnancies may be possible in some of these women, no live births or ongoing pregnancies have been reported to date., (Copyright © 2023 Reproductive Healthcare Ltd. All rights reserved.)

Bee venom with an antimicrobial effect is a powerful natural product. One of the most important areas where new antimicrobials are needed is in the prevention and control of multi-drug resistant pathogens. Today, antibacterial products used to treat multi-drug resistant pathogen infections in hospitals and healthcare facilities are insufficient to prevent colonisation and spread, and new products are needed. The aim of the study is to investigate the antibacterial effect of the bee venom (BV), a natural substance, on the species of Methicillin resistant Staphylococcus aureus, Vancomycin resistant Enterococcus faecalis, Carbapenem resistant Escherichia coli, Carbapenem resistant Klebsiella pneumoniae and Carbapenem resistant Acinetobacter baumannii. As a result of this study, it was found that MIC90 and MBC90 values ranged from 6.25 μg/mL - 12.5 μg/mL and numbers of bacteria decreased by 4-6 logs within 1-24 h for multi-drug resistant pathogens. In particular, Vancomycin resistant Enterococcus faecalis isolate decreased 6 log cfu/mL at 50 μg/mL and 100 μg/mL concentrations in the first hour. The effective bacterial inhibition rate of bee venom suggests that it could be a potential antibacterial agent for multi-drug resistant pathogens.Contribution: The treatment options of antibiotic-resistant pathogens are a major problem in both veterinary and human medicine fields. We have detected a high antibacterial effect against these agents in this bee venom study, which is a natural product. Apitherapy is a fashionable treatment method all over the world and is used in many areas of health. Bee venom is also a product that can be used as a drug or disinfectant raw material and can fill the natural product gap that can be used against resistant bacteria.

Objective: Coronavirus disease 2019 emerges as a disease caused by severe acute respiratory syndrome coronavirus 2. It is a systemic disease associated with vascular inflammation and endothelial damage. In this study, we aimed to investigate whether vascular endothelial growth factor gene insertion/deletion polymorphism is associated with coronavirus disease 2019 in the Turkish population., Methods: The study included 179 participants (79 patients with coronavirus disease 2019 and 100 controls). DNA isolation was made from peripheral blood, and then the polymerase chain reaction analysis was performed., Results: When we analyze vascular endothelial growth factor gene insertion/deletion polymorphism in the study group, we found that the DD genotype and D allele were found to be statistically significantly different when compared to coronavirus disease 2019 patients with high vitamin D value (p=0.005 for DD genotype and p=0.006 for D allele) in the control group. In this high-level control group, when we analyze II+ID genotype versus DD, a statistically significant difference was also detected (p=0.007)., Conclusion: As a result of the study, we found that DD genotype and D allele were associated with vitamin D level in Turkish patients with coronavirus disease 2019.

Kaya-Barakat-Masson syndrome (KABAMAS) is a recently identified severe neurodevelopmental disorder characterized by severe global developmental delay, epilepsy, movement disorder, epilepsy, and microcephaly. KABAMAS is caused by bi-allelic variants in the YIF1B gene which encodes a trafficking protein involved in the anterograde traffic from the endoplasmic reticulum to the cell membrane including neural cells in association with other trafficking proteins and also Golgi apparatus morphology. That's why clinical overlapping between KABAMAS and golgipathies isn't surprising. It is a rare condition with only 24 patients reported to date. Here we described a 5.5-year-old boy presenting with severe global developmental delay, epileptic encephalopathy, microcephaly, dystonia, spasticity, blindness, feeding difficulties, respiratory failure, and dysmorphic features. Whole exome sequencing identified homozygous splice site variation (NM_001039672.3: c.297+1G > A) in the YIF1B gene. This splice site variant is rare in the general population (gnomAD Variant allele fraction (VAF): 0.0007%, 2 heterozygotes, 0 homozygotes) and has not previously been associated with the disease. Multiple in silico tools predict a deleterious effect of this splice site change. Considering the points mentioned above, we have considered the detected variant as pathogenic according to guidelines in light of current knowledge. By reporting a new case with the homozygous YIF1B splice site variant we provide further evidence to clinical and molecular data of this recently recognized severe neurodevelopmental disorder. We further emphasize that trafficking errors should be considered as an underlying mechanism in undiagnosed severe neurodevelopmental disorders., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: The negative effects of pretransplant obesity and post-transplant body mass index (BMI) increase on graft survival have been reported in recent years. The aim of this study is to evaluate the effects of BMI changes on post-transplant graft function, lipid profile, and blood pressure., Methods: The study included 133 pediatric patients transplanted between 1994 and 2019 in Ege University. BMI Z-scores (BMIZs) were calculated according to age and sex before and after transplantation using the World Health Organization criteria. Patients with BMIZs >+1 standard deviation (SD) were defined as overweight, and those with BMIZs >+2 SD were defined as obese: Group 1: Obese or overweight before transplantation; Group 2: Thin or normal weight before and 2 years after transplantation; and Group 3: Thin or normal weight before transplantation and obese or overweight 2 years after transplantation., Results: At the time of transplantation 8% of the patients were overweight, and 1% were obese. Overweight and obesity statistically significantly increased (31.6%) 2 years after renal transplantation (P = .001). Obese and overweight patients have lower high-density lipoprotein levels and were younger at the time of transplantation. Graft functions, lipid levels, and blood glucose levels of the groups were similar (P > .05). The only significant difference between the groups was that Group 1 patients were younger than Group 2., Conclusions: Obesity develops at a significant rate in pediatric patients after renal transplantation. In this study, we could not demonstrate negative effects of obesity and being overweight in terms of post-transplant graft function, lipid profile, blood glucose, and blood pressure., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: One of the causes of infertility is circadian rhythm disorders. This study aimed to investigate Clock 3111 T/C and Period3 VNTR (variable number tandem repeat) gene polymorphisms and these gene proteins, some biochemical parameters, and circadian rhythm hormones in infertile women., Methods: Thirty-five infertile women and thirty-one healthy fertile women were included. Blood samples were taken in the mid-luteal phase. DNAs obtained from peripheral blood were analyzed using polymerase chain reaction-restriction fragment length polymorphism methods. Follicle-stimulating hormone, LH (luteinizing hormone), estradiol, prolactin, free triiodothyronine, fT4 (free thyroxine), thyroid-stimulating hormone, testosterone, cortisol, progesterone, prolactin, ferritin, vitamin B12, and folate levels in serum samples were determined by the electrochemiluminescence immunoassay method. Melatonin, Clock, and Period3 protein levels were determined with ELISA kits., Results: There was a significant difference in the frequency of Period3 DD (Per3 4/4 ) genotype between the groups. The Clock protein level of the infertile group was higher than the fertile group. Clock protein levels of the fertile group were positively correlated with estradiol levels and negatively correlated with LH, prolactin, and fT4 levels. PER3 protein levels of the infertile group were negatively correlated with LH levels. Melatonin levels of the fertile group were positively correlated with progesterone levels and negatively correlated with cortisol levels. Melatonin levels of the infertile group were positively correlated with LH levels and negatively correlated with cortisol levels., Conclusion: Per3 4/4 genotype may be an independent risk factor in infertile women. Different correlation results found in fertile and infertile women can form the basis for future studies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this study, precipitation; temperature (maximum, minimum, and average temperature) values of Eskişehir, Konya, Afyonkarahisar, Uşak, and Kütahya for years (2007-2018); and protein content, macro sedimentation (MSDS), thousand kernel weight (KW), test weight (TW) relations, and the effect of climate values on quality were investigated. The Kriging method was used by ArcGIS software for creating quality maps of Eskişehir, Konya, Afyonkarahisar, Uşak, and Kütahya provinces in the light of obtained data from these examined quality criteria, yield, and climate factors. The quality of bread wheat, which includes protein content, macro sedimentation, thousand kernel weight, and test weight, is highly affected by the subject precipitation, maximum temperature, minimum temperature, average temperature, and precipitation. While the months of November, March, and April and the total annual precipitations affect the quality, the most effective precipitation is the months of April and November. Again, the fact that the winter months are hot, especially in January and February, causes the plant to be inadequate to withstand the winter, causing the plant to be more affected by the low temperatures in the early spring and to reduce the quality due to insufficient plant growth. Climatic factors affect quality in total, not alone, but cumulatively. It was concluded that the best quality wheat can be obtained from Konya, Eskişehir, and Afyonkarahisar provinces. It was concluded that ESOGÜ quality index (EQI), evaluating and integrating protein content, macro sedimentation, thousand kernel weight, and test weigh together, can be used safely in bread wheat genotypes., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background:  Rotavirus is known to be one of the most common infections, usually associated with severe diarrhea. Despite the existence of two licensed vaccines, many countries, including Turkey, have not included rotavirus vaccination in their nationally funded vaccination program. This article explores what factors influence parents' decisions about whether to have their children vaccinated against rotavirus and which factors changed from 2010 through 2016., Materials and Methods:  Data were collected over two periods via questionnaires. The first period was from January 2009 through March 2010, and data were gathered from a semi-private pediatric outpatient clinic in Kocaeli, Turkey. The second period was from August 2015 through May 2016, and data were collected from parents during their pediatric outpatient clinic visits. Two questionnaires were designed to find out the rotavirus vaccination status of the children, socio-demographic factors, and reasons for excluding/accepting the rotavirus vaccine. The level of knowledge about the rotavirus vaccine was investigated. Parents indicated their level of agreement with each statement using a five-point Likert scale., Results:  While only 3.8% of the parents accepted the rotavirus in 2009-2010, it increased to 69.5% in 2015-2016. Significant factors influencing parents' decision to vaccinate their children for rotavirus were advice from a pediatrician, a lack of correct and timely rotavirus information, and the cost of the vaccine., Conclusions:  The acceptance of the rotavirus vaccine depends on parental perceptions, which may be influenced by accurate and timely information, the advice of their healthcare provider, and inclusion in the nationally funded vaccination program. In contrast to other studies reported, the education level of the mothers and fathers and their job types appear to be important. It was also found that parents' attitudes and perceptions changed over time., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Gundogdu et al.)

Thrombotic and microangiopathic effects have been reported in COVID-19 patients. This study examined the contribution of the hereditary thrombophilia factors Prothrombin (FII) and Factor V Leiden (FVL) genotypes to the severity of COVID-19 disease and the development of thrombosis. This study investigated FII and FVL alleles in a cohort of 9508 patients (2606 male and 6902 female) with thrombophilia. It was observed that 930 of these patients had been infected by SARS-CoV-2 causing COVID-19. The demographic characteristics of the patients and their COVID-19 medical history were recorded. Detailed clinical manifestations were analyzed in a group of cases (n = 4092). This subgroup was age and gender-matched. FII and FVL frequency data of healthy populations without thrombophilia risk were obtained from Bursa Uludag University Medical Genetic Department's Exome Databank. The ratio of males (31.08%; 27.01%) and the mean age (36.85 ± 15.20; 33.89 ± 14.14) were higher among COVID-19 patients compared to non-COVID-19 patients. The prevalence of FVL and computerized tomography (CT) positivity in COVID-19 patients was statistically significant in the thrombotic subgroup (p < 0.05). FVL prevalence, CT positivity rate, history of thrombosis, and pulmonary thromboembolism complication were found to be higher in deceased COVID-19 patients (p < 0.05). Disease severity was mainly affected by FVL and not related to genotypes at the Prothrombin mutations. Overall, disease severity and development of thrombosis in COVID-19 are mainly affected by the variation within the FVL gene. Possible FVL mutation should be investigated in COVID-19 patients and appropriate treatment should be started earlier in FVL-positive patients., (© 2023 Wiley Periodicals LLC.)

Objective: Familial Mediterranean fever (FMF) is one of the most common inherited autoinflammatory diseases. Angiogenesis is a feature of inflammatory activation and part of pathogenic processes in autoimmune diseases. Therefore, this study aimed to investigate the role of the Vascular endothelial growth factor ( VEGF ) gene insertion/deletion (I/D) functional variant in FMF Turkish patients. Methods: MEFV gene mutations were detected in all patients. The FMF patients (N:105) and the healthy controls (N:100) were genotyped for the VEGF I/D variant using PCR followed by agarose gel electrophoresis. The results were statistically analyzed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ 2 -tests. Results: The mean age of patients was 25.46 ± 10.09. Fifty-nine patients (56.2%) had two or more MEFV gene mutations. The most common MEFV mutation was M694V/M694V. The VEGF I/D variant genotype distribution exhibited a statistically significant difference between the patients and the controls. VEGF I/D genotype was higher in controls compared to patients, while D/D genotype was higher in patients compared to the controls (p = 0.003 , p = 0.013 , respectively). When we examined the clinical findings, joint pain was more common in patients with VEGF D/D and I/D genotypes compared to I/I genotype ( p = 0.043 ). Although not statistically significant, the most common genotype in patients with two or more MEFV mutations was VEGF D/D (28.6%). Conclusion: The results provided evidence supporting that the D/D genotype of the VEGF I/D variant is associated with an increased risk of FMF in a group of Turkish populations.

Heterogeneity in symptoms associated with COVID-19 in infected patients remains unclear. ACE2 and TMPRSS2 gene variants are considered possible risk factors for COVID-19. In this study, a retrospective comparative genome analysis of the ACE2 and TMPRSS2 variants from 946 whole-exome sequencing data was conducted. Allele frequencies of all variants were calculated and filtered to remove variants with allele frequencies lower than 0.003 and to prioritize functional coding variants. The majority of detected variants were intronic, only two ACE2 and three TMPRSS2 nonsynonymous variants were detected in the analyzed cohort. The main ACE2 variants that putatively have a protective or susceptibility effect on SARS-CoV-2 have not yet been determined in the Turkish population. The Turkish genetic makeup likely lacks any ACE2 variant that increases susceptibility to SARS-CoV-2 infection. TMPRSS2 rs75603675 and rs12329760 variants that were previously defined as common variants that have different allele frequencies among populations and may have a role in SARS-CoV-2 attachment to host cells were determined in the population. Overall, these data will contribute to the formation of a national variation database and may also contribute to further studies of ACE2 and TMPRSS2 in the Turkish population and differences in SARS-CoV-2 infection among other populations., (© 2022 Wiley Periodicals LLC.)

Femoral nerve palsy and meralgia paresthetica following gynecologic cancer surgery are rare, but severe and long lasting. Here, we aimed to study their incidence, severity, possible risk factors and its time to remission. Between January 2008 and December 2017 976 gynecologic cancer patients were identified in our institutional database receiving surgery. Complete patient charts were reviewed retrospectively. Possible risk factors were analyzed by Fisher's exact test. 441 (45.18%) out 976 were treated for Ovarian cancer. In total 23 patients were identified with a postoperative neurological leg disorder. A femoral nerve palsy was present in 15 patients (1.5%) and a meralgia paresthetica in 8 patients (0.82%). Three patients showed both disorders. Duration of surgery ( p = 0.0000), positioning during surgery ( p = 0.0040), femoral artery catheter ( p = 0.0051), prior chemotherapy ( p = 0.0007), nicotine abuse ( p = 0.00456) and prior polyneuropathy ( p = 0.0181) showed a significant association with a postoperative femoral nerve palsy. Nicotine abuse ( p = 0.0335) and prior chemotherapy ( p = 0.0151) were significant for the development of a meralgia paresthetica. Long lasting surgery, patient positioning and femoral arterial catheter placement are risk factors for a postoperative femoral nerve palsy in gynecologic cancer surgery. Polyneuropathy, nicotine abuse, and prior chemotherapy are predisposing risk factors for a femoral nerve palsy and a meralgia paresthetica. A resolution of symptoms is the rule for both disorders within different time schedules.

Balanced vaginal microbiota and, as a continuum, cervical canal microbiota help prevent reproductive disorders, including recurrent miscarriage (RM). In a significant proportion of couples with RM, routine diagnostic workup cannot find any manageable cause, leading to a requirement for new diagnostic tools. In the present study, we determined the quantitative composition of the microbiota of the vagina and cervical canal, assessed by real-time polymerase chain reaction, in women with RM. It also evaluated their derangements related to the pathogenesis of RM, and thus the suitability of this test as a diagnostic tool for managing RM. Vaginal and cervical canal specimens of 25 women with RM and 25 healthy volunteers were collected. The test results revealed information about the total vaginal bacterial biomass by measuring the abundance of Lactobacillus spp.; other bacteria; and pathogens, including Mycoplasma hominis , Mycoplasma genitalium , Ureaplasma (urealyticum + parvum) , and Candida spp. Overall, the findings of this study implied the abundance of Lactobacillus spp. decreased in women with RM with an increase in the abundance of other microorganisms in accordance with the reduction in the abundance of Lactobacillus spp. due to aerobic vaginitis and bacterial vaginosis. Vaginal and cervical canal microbiota need to be considered during the diagnostic workup of women with RM.IMPACT STATEMENT What is already known on this subject? Recurrent miscarriage (RM) is a well-known reproductive disorder. Its diagnostic workup is not successful in determining the underlying problem in many cases. Hence, novel diagnostic tools based on real-time polymerase chain reaction (PCR) are needed for evaluating reproductive microbiota, which are considerably reliable, to satisfy the expectations of women with RM. What do the results of this study add? Overall, the decrease in the abundance of Lactobacillus spp. was found to be related to RM, and the patterns of the presence of other microorganisms were in accordance with the reduction in the abundance of Lactobacillus spp. These findings suggested an important role of vaginal and cervical canal microbiota in the pathogenesis of RM. What are the implications of these findings for clinical practice and/or further research? Additional research is warranted to elucidate the functional impact of altered components of the microbiota of vaginal and cervical canals on the physiology of the local cervical canal and its participation in the microbiota of the endometrial cavity, especially regarding unsuccessful pregnancies as a result of the disturbed physiology of the local endometrial microenvironment. However, possible applications of real-time PCR-based tests for the screening of subclinical infections in clinical practice require the performance of further investigations in patients with RM.

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.)

Impression management is a fundamental aspect of social life. From self-promotion to feedback giving, from advice seeking to networking, people frequently find themselves in situations where they need to make a positive impression on others. Despite the long-term benefits of making a favorable impression, impression management attempts can backfire in unintended ways. In this article, I review recent research on self-presentation, social cognition, and communication to explain when and why people have misguided intuitions about their impressions on others, document common impression management mistakes, and propose more effective strategies to minimize actor-target asymmetries in social interactions. This review provides a theoretical framework to understand the psychology of impression (mis)management, as well as the risks and rewards of different self-presentation strategies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This was a retrospective analysis of liver transplant for pediatric patients with liver cirrhosis and hepatocellular carcinoma., Materials and Methods: Fourteen pediatric patients with chronic liver disease and hepatocellular carcinoma underwent liver transplant from 2004 to 2021. Preexisting diseases were tyrosinemia (n = 6), progressive familial intrahepatic cholestasis type 2 (n = 2) and type 3 (n = 3), cryptogenic cirrhosis (n = 2), hepatitis B and D (n = 1), and biliary atresia (n = 1)., Results: Mean age was 9.43 ± 4.9 years (range, 13 months to 16 years). Three patients had 1 tumor, 4 had 2 tumors, and 7 had multiple (≥3) lesions. Six patients were classified as Pretreatment Extent of Disease Staging System for Hepatoblastoma (PRETEXT) stage IV, 3 as stage II, and 5 as stage I. Some patients received systemic chemotherapy before (n = 4) or after transplant (n = 3) or transarterial chemoembolization and microwave ablation pretransplant (n = 1). Hepatocellular carcinoma posttransplant recurrence was observed at 23, 47, and 108 months in 3 patients (21%). Recurrence sites were omentum (n = 1) and liver graft (n = 2). One patient was treated with hepatic resection, radiofrequency ablation, and radiotherapy, while the other received radiofrequency ablation and chemotherapy for graft tumor recurrence. Relapse-free patient survival rates were 92%, 82.5%, and 72.2% at 2, 4, and 10 years, respectively. Four recipients (28.5%) died; posttransplant cause of death was infection at 19 (n = 1) and 188 months (n = 1) or hepatocellular carcinoma recurrence at 79 (n = 1) and 165 months (n = 1). Median follow-up was 178 months (range, 13-204 months). Mean estimated survival was 171.25 ± 16.6 months. Overall patient posttransplant survival was 100%, 92.3%, 92.3%, 83%, and 72% at 1, 2, 5, 10, and 15 years, respectively., Conclusions: Hepatocellular carcinoma was mainly associated with inherited liver diseases in our pediatric series. Liver transplant provided a long-term survival advantage to pediatric patients with preexisting cirrhosis and hepatocellular carcinoma.

Aim: Microbiota of the reproductive tract may be associated with unexplained infertility in women. We aimed to determine the derangements of vaginal and endometrial microbiota related to unexplained infertility by real-time polymerase chain reaction (real-time PCR) microbiota analyses of vaginal and endometrial samples of the unexplained infertility patients and fertile women., Materials and Methods: Twenty-six women with unexplained infertility and 26 age-matched fertile women were included. Vaginal and endometrial samples were obtained in the mid-menstrual cycle for analysis by quantitative real-time PCR method., Results: The proportion of lactobacilli-impaired microbiota was significantly higher in the vaginal samples of unexplained infertility patients (76.9% vs. 26.9%; p < 0.001). Those with impaired lactobacilli microbiota of vaginal samples had an increased risk of 9.048 times for infertility than those with normal lactobacilli microbiota. In addition, the mean lactobacilli/total bacterial mass (TBM) ratio in the vaginal samples was significantly lower in the unexplained infertility patients (38.2% vs.76.3%; p = 0.001)., Conclusion: The present study results supported the role of vaginal and endometrial microbiota derangements in unexplained infertility. Many time-consuming and invasive methods are currently used in the diagnosis of infertility. Our study showed that the quantitative determination of lactobacilli/TBM ratio in vaginal specimens, a less invasive and easily obtainable method, could be used as a diagnostic test during the workup of couples with unexplained infertility., (© 2021 Japan Society of Obstetrics and Gynecology.)

Neurodevelopmental disorders (NDDs) are clinically and genetically heterogenous; many such disorders are secondary to perturbation in brain development and/or function. The prevalence of NDDs is > 3%, resulting in significant sociocultural and economic challenges to society. With recent advances in family-based genomics, rare-variant analyses, and further exploration of the Clan Genomics hypothesis, there has been a logarithmic explosion in neurogenetic "disease-associated genes" molecular etiology and biology of NDDs; however, the majority of NDDs remain molecularly undiagnosed. We applied genome-wide screening technologies, including exome sequencing (ES) and whole-genome sequencing (WGS), to identify the molecular etiology of 234 newly enrolled subjects and 20 previously unsolved Turkish NDD families. In 176 of the 234 studied families (75.2%), a plausible and genetically parsimonious molecular etiology was identified. Out of 176 solved families, deleterious variants were identified in 218 distinct genes, further documenting the enormous genetic heterogeneity and diverse perturbations in human biology underlying NDDs. We propose 86 candidate disease-trait-associated genes for an NDD phenotype. Importantly, on the basis of objective and internally established variant prioritization criteria, we identified 51 families (51/176 = 28.9%) with multilocus pathogenic variation (MPV), mostly driven by runs of homozygosity (ROHs) - reflecting genomic segments/haplotypes that are identical-by-descent. Furthermore, with the use of additional bioinformatic tools and expansion of ES to additional family members, we established a molecular diagnosis in 5 out of 20 families (25%) who remained undiagnosed in our previously studied NDD cohort emanating from Turkey., Competing Interests: Declaration of interests J.R.L. has stock ownership in 23andMe, is a paid consultant for the Regeneron Genetics Center, and is a co-inventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing conducted at Baylor Genetics (BG) Laboratories. J.R.L. serves on the Scientific Advisory Board of BG. Other authors have no potential conflicts to report., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism may play a role in the pathogenesis of coronavirus-19 disease (COVID-19)., Objectives: Investigate the relationship between ACE I/D polymorphism and the clinical severity of COVID-19., Design: Prospective cohort study., Setting: Tertiary care hospital., Patients and Methods: The study included COVID-19 patients with asymptomatic, mild, and severe disease with clinical data and whole blood samples collected from 1 April 2020 to 1 July 2020. ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis., Main Outcome Measure: ACE DD, DI and II genotypes frequencies., Sample Size: 90 cases, 30 in each disease severity group., Results: Age and the frequency of general comorbidity increased significantly from the asymptomatic disease group to the severe disease group. Advanced age, diabetes mellitus and presence of ischemic heart disease were independent risk factors for severe COVID-19 [OR and 95 % CI: 1.052 (1.021-1.083), 5.204 (1.006-26.892) and 5.922 (1.109-31.633), respectively]. The ACE II genotype was the dominant genotype (50%) in asymptomatic patients, while the DD genotype was the dominant genotype (63.3 %) in severe disease. The ACE II geno-type was protective against severe COVID-19 [OR and 95% CI: .323 (.112-.929)]. All nine patients (8.9%) who died had severe disease., Conclusions: The clinical severity of COVID-19 infection may be associated with the ACE I/D polymorphism., Limitations: Small sample size and single center., Conflict of Interest: None.

Self-promotion is common in everyday life. Yet, across 8 studies (N = 1,687) examining a broad range of personal and professional successes, we find that individuals often hide their successes from others and that such hiding has relational costs. We document these effects among close relational partners, acquaintances, and within hypothetical relationships. Study 1 finds that targets feel less close to and more insulted by communicators who hide rather than share their successes. Study 2 finds that hiding success harms relationships both when the success is eventually discovered and when it is not. Studies 3 and 4 explore the mechanism underlying these relational costs: Targets infer that communicators have paternalistic motives when they hide their success, which leads them to feel insulted. Studies 5-7 explore the contextual cues that elicit inferences of paternalistic motives, such as private (vs. public) settings (Study 5), direct (vs. indirect) questions (Study 6), and close (vs. distant) relationships (Study 7). Across our studies, we also explore the emotional and impression-management consequences of hiding success. Although the relational consequences of hiding success are universally negative, the emotional and impression-management consequences are mixed. Whereas previous research highlights the negative consequences of sharing one's accomplishments with others, we find that sharing is superior to hiding for maintaining one's relationships. Thus, we shed new light on the consequences of paternalism and the relational costs of hiding information in everyday communication. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Fabry Disease (FD, OMIM#301500) is a progressive, life-threatening, multisystemic, rare lysosomal storage disease. Today, approximately 1000 mutations are recorded in the Human Gene Mutation Database (www.hgmd.org) for GLA. Among the identified mutations, genetic variants of unknown significance (GVUS) and novel mutations cause problems in terms of diagnosis and treatment approach., Methods: In our study, 510 high-risk patients were enrolled. 229 out of 510 were Male (45%) (Mean age was 40.8 ±15.0) and 281 of were Female (55%) (Mean age was 39, 7±15.5). The definite diagnosis of the FD was confirmed by GLA gene sequence analysis. GLA mutation was found in 15 cases (3.4%). Family members of the relevant indexes were included in the screening programs according to the X-linked inheritance pattern. And then we conducted family screening on 74 family members of 15 index cases. Of those 74 cases, 39 had mutations (53%). In males, α-GalA activity and in both gender Lyso-Gb3 levels were measured and multisystem evaluation was performed in all cases with the mutation., Results: We found six different familial mutation types; two of them pathogenic; p.D170N (1), p.P205S (13), one of them GVUS; p.Q330R (1), three of them likely benign; p.D313Y (12), p.S126G (25), c.-30G>A (2) mutations were detected., Conclusion: The purpose of this retrospective study is to approach Fabry disease on a genetic basis and to improve its management and to draw attention to the importance of early diagnosis. We also aimed to evaluate the appropriate algorithms to determine whether the mutation is the FD-causing mutation or not., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: In this retrospective study, we aimed to determine the most common infectious agents in infants within the first 6 months of liver transplant., Materials and Methods: Thirty-four infant patients with median age of 8 months (range, 4-12 mo) at the time of liver transplant were retrospectively evaluated. We evaluated causative organisms in bloodstream cultures and in subclavian catheter, urine, and intra-abdominal drainage fluid cultures. We also evaluated Epstein-Barr and cytomegalovirus infections by polymerase chain reaction in all recipients., Results: The most common isolated bacteria from the bloodstream were Klebsiella pneumoniae, Staphylococcus epidermidis, and Enterococcus faecium. Staphylococcus epidermidis was the most common isolated bacteria from subclavian catheter cultures. Klebsiella pneumoniae was the most common bacteria isolated from intra-abdominal drainage fluid. Only 1 recipient had cytomegalovirus infection during this period., Conclusions: Our study showed a high incidence of Klebsiella pneumoniae infections in infants after liver transplant. New prophylactic antibiotic strategies can be promoted to prevent Klebsiella pneumoniae infections in infants.

Objectives: Liver transplant is currently the most effective option for patients with end-stage liver disease. Seizures are the most common neurologic complication after liver transplant. Posterior reversible encephalopathy syndrome is a neurologic syndrome characterized by lethargy, seizures, visual disturbances, and radiologic findings of edema in the posterior regions of the cerebral hemispheres. Levetiracetam is prescribed for a broad spectrum of seizure types but does not have a specific indication for epilepsy in children after solid-organ transplant. Our aim was to investigate the efficacy and tolerability of levetiracetam in pediatric transplant recipients with posterior reversible encephalopathy syndrome and epilepsy., Materials and Methods: We reviewed records of patients treated for epilepsy due to posterior reversible encephalopathy syndrome after liver transplant seen at our pediatric neurology clinic between January 2010 and March 2019. Patients were assessed clinically and by neurologic examination, electroencephalography, and cerebral magnetic resonance imaging., Results: Among 134 children who had undergone liver transplant between 2010 and 2019, 10 patients (6 males, 4 females; age range,7-19 y) who were diag-nosed with posterior reversible encephalopathy syndrome and epilepsy were included in the study. All patients received levetiracetam at 20 mg/kg/day. After a mean follow-up of 28.9 months (range, 24-40 mo), 9 patients (90%) attained complete seizure freedom. One patient who had an underlying neurodegenerative disease (hemophagocytic syndrome) other than posterior reversible encephalopathy syndrome continued to have seizures under levetiracetam treatment. One patient had a mild adverse reaction (irritability) due to levetiracetam but did not require drug discontinuation., Conclusions: In this study, 90% of patients with posterior reversible encephalopathy syndrome became seizure free with levetiracetam treatment. Our findings suggest that levetiracetam has a favorable efficacy for epilepsy due to posterior reversible encephalopathy syndrome in pediatric liver transplant recipients with tolerable adverse effects.

This phase 3 trial compared tandem autologous stem cell transplantation (autoSCT) versus autoSCT followed by reduced-intensity conditioning allogeneic stem cell transplantation (auto/alloSCT) in patients with newly diagnosed multiple myeloma (MM) with deletion of (del) chromosome 13q (del13q). The availability/absence of a human leukocyte antigen-matched-related or matched-unrelated donor (MUD) determined the nature of the second SCT. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population (n = 199). Auto/alloSCT was performed in 126 patients; 74 received MUD allografts. After 91 months median follow-up, median PFS with auto/allo versus tandem autoSCT was 34.5 versus 21.8 months (P = 0.003; adjusted hazard ratio 0.55, 95% confidence interval 0.36-0.84). Median overall survival (OS) was 70.2 versus 71.8 months (P = 0.856). Two-year non-relapse mortality with auto/allo versus tandem autoSCT was 14.3% versus 4.1% (P = 0.008). In patients harboring both del13q and del17p, median PFS and OS were 37.5 and 61.5 months with auto/allo (n = 19) versus 6.1 and 23.4 months with tandem autoSCT (n = 6) (P = 0.0002 and 0.032). Our findings suggest that auto/alloSCT significantly extends PFS versus tandem autoSCT in del13q MM, and indicate some survival benefit for first-line alloSCT in high-risk MM.

Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are alarming in the clinical setting, as CRE isolates often exhibit resistance to most clinically-available antibiotics. Klebsiella pneumoniae carbapenemase (KPC) is the most common carbapenemase carried by CRE in North America and Europe, frequently detected in isolates of K. pneumoniae, Escherichia coli, and Enterobacter cloacae. Notably, KPC-expressing strains often arise from clonal lineages, with sequence type 258 (ST258) representing the dominant lineage in K. pneumoniae, ST131 in E. coli, and ST78 and ST171 in E. cloacae. Prior studies have demonstrated that carbapenem-resistant K. pneumoniae differs from carbapenem-susceptible K. pneumoniae at both the transcriptomic and soluble metabolomic levels. In the present study, we sought to determine whether carbapenem-resistant and carbapenem-susceptible isolates of K. pneumoniae, E. coli, and E. cloacae produce distinct volatile metabolic profiles. We were able to identify a volatile metabolic fingerprint that could discriminate between CRE and non-CRE with an area under the receiver operating characteristic curve (AUROC) as high as 0.912. Species-specific AUROCs were as high as 0.988 for K. pneumoniae and 1.000 for E. cloacae. Paradoxically, curing of KPC-expressing plasmids from a subset of K. pneumoniae isolates further accentuated the metabolic differences observed between ST258 and non-ST258.

Introduction: The most important complication of familial Mediterranean fever (FMF) is secondary amyloidosis, which can lead to kidney failure. Genetic variability in the genes of various components of the renin-angiotensin system may play a role in the pathogenesis of the kidney disorders.  The aim of the present study was to investigate the association between angiotensin converting enzyme (ACE) gene I/D variant and risk of developing FMF-related amyloidosis in Turkish patients., Materials and Methods: A total of 240 individuals consisting of 40 patients with FMF-related amyloidosis, 100 FMF patients without amyloidosis, and 100 healthy controls were recruited. For all of the participants, ACE I/D variant was detected by the polymerase chain reaction using specific primers., Results: A significant difference was found between the patients with FMF-related amyloidosis and the control group as for genotype distribution of ACE I/D variant (P < .05). The ACE D/D and I/D genotypes were more frequent in the patients with FMF-related amyloidosis while the I/I genotype was less frequent in the same patients. The FMF patients (with and without amyloidosis) had significantly higher percentages of the D/D and I/D genotypes than the healthy controls (P < .05). Comparison between the subgroups of FMF patients, divided into those with and without amyloidosis, yielded a significant correlation according to ID+II versus DD genotypes (P < .03, odds ratio, 3.24; 95% confidence interval, 1.05 to 12.01).  Conclusions. Based on these observations, the ACE I/D variant D/D genotypes implicate a possible risk in the FMF-related amyloidosis among Turkish population.

Background: Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in homocysteine (Hcy) metabolism. We aimed to evaluate a possible relationship between MTHFR gene C677T (rs 1801133), A1298C (rs 1801131) variants and susceptibility to FMF in a Turkish cohort., Material-Methods: This case-control study included 198 Turkish FMF patients and 100 healthy subjects as controls. MTHFR C677T and A1298C were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) methods., Results: The genotype distribution and allele frequency of the MTHFR C677T were statistically different between the patients and the control group (P=.006, P=.001, respectively). The frequency of the TT genotype and T allele of MTHFR C677T was significantly higher in the patients than in the controls. The genotype distribution of MTHFR A1298C variant did not show any statistically significant difference between the patients and the controls (P›.05). The patients had statistically different frequencies in allele C of MTHFR A1298C variant compared with the control (P=.032). We also examined the risk associated with inheriting the combined genotypes for the two MTHFR variants. According to these results, individuals who were CC homozygous at C677T locus and AA homozygous at A1298C locus have a lower risk of developing FMF (P=.002). Individuals who were TT homozygous at C677T locus and AC heterozygous at A1298C locus have higher risk of developing FMF (P=.033)., Conclusion: Our findings clearly showed there was an association the MTHFR C677T/A1298C variants and susceptibility to FMF in the Turkish sample., (© 2017 Wiley Periodicals, Inc.)

Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on high-dose radiation, but studies exploring the potential benefit of systemic therapies for high-risk patients are urgently needed. In this review, a panel of expert European hematologists updates the recommendations on the diagnosis and management of patients with solitary plasmacytoma.

Self-presentation is a fundamental aspect of social life, with myriad critical outcomes dependent on others' impressions. We identify and offer the first empirical investigation of a prevalent, yet understudied, self-presentation strategy: humblebragging. Across 9 studies, including a week-long diary study and a field experiment, we identify humblebragging-bragging masked by a complaint or humility-as a common, conceptually distinct, and ineffective form of self-presentation. We first document the ubiquity of humblebragging across several domains, from everyday life to social media. We then show that both forms of humblebragging-complaint-based or humility-based-are less effective than straightforward bragging, as they reduce liking, perceived competence, compliance with requests, and financial generosity. Despite being more common, complaint-based humblebrags are less effective than humility-based humblebrags, and are even less effective than simply complaining. We show that people choose to deploy humblebrags particularly when motivated to both elicit sympathy and impress others. Despite the belief that combining bragging with complaining or humility confers the benefits of each strategy, we find that humblebragging confers the benefits of neither, instead backfiring because it is seen as insincere. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m 2 intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression-free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival., (© 2017 John Wiley & Sons Ltd.)

Conventional cytomorphologic assessment is the first step to establish an accurate diagnosis in urinary cytology. In cytologic preparations, the separation of low-grade urothelial carcinoma (LGUC) from reactive urothelial proliferation (RUP) can be exceedingly difficult. The bladder washing cytologies of 32 LGUC and 29 RUP were reviewed. The cytologic slides were examined for the presence or absence of the 28 cytologic features. The cytologic criteria showing statistical significance in LGUC were increased numbers of monotonous single (non-umbrella) cells, three-dimensional cellular papillary clusters without fibrovascular cores, irregular bordered clusters, atypical single cells, irregular nuclear overlap, cytoplasmic homogeneity, increased N/C ratio, pleomorphism, nuclear border irregularity, nuclear eccentricity, elongated nuclei, and hyperchromasia (p ˂ 0.05), and the cytologic criteria showing statistical significance in RUP were inflammatory background, mixture of small and large urothelial cells, loose monolayer aggregates, and vacuolated cytoplasm (p ˂ 0.05). When these variables were subjected to a stepwise logistic regression analysis, four features were selected to distinguish LGUC from RUP: increased numbers of monotonous single (non-umbrella) cells, increased nuclear cytoplasmic ratio, hyperchromasia, and presence of small and large urothelial cells (p = 0.0001). By this logistic model of the 32 cases with proven LGUC, the stepwise logistic regression analysis correctly predicted 31 (96.9%) patients with this diagnosis, and of the 29 patients with RUP, the logistic model correctly predicted 26 (89.7%) patients as having this disease. There are several cytologic features to separate LGUC from RUP. Stepwise logistic regression analysis is a valuable tool for determining the most useful cytologic criteria to distinguish these entities., (© 2017 APMIS. Published by John Wiley & Sons Ltd.)

Background: Adverse outcomes of pregnancy are a challenging health-care problem. Prediction of adverse pregnancy outcomes is important to prevent the morbidities of the foetus and the mother., Aims: To study the clinical interest of fetal nasal bone length in predicting adverse pregnancy outcomes in the first trimester of pregnancy., Study Design: A population-based retrospective cohort study., Methods: Data from 868 women with first-trimester fetal nasal bone length and birth records available were enrolled. Fetal nasal bone length percentiles were determined and evaluated for their ability to predict adverse pregnancy outcomes such as preterm birth, preterm labour, preterm premature rupture of membranes, early preterm birth, gestational diabetes mellitus, gestational hypertension-preeclampsia, small-for-gestational age foetuses, macrosomia, oligohydramnios, polyhydramnios and fetal distress., Results: Fetal nasal bone length >95th percentile was significantly associated with preterm labor and preterm premature rupture of membranes (p=0.02, accuracy 0.91 and p=0.001, accuracy 0.94, respectively), whereas nasal bone length >99th percentile was significantly associated with preterm labor and oligohydramnios (p=0.006, accuracy 0.95 and p=0.014, accuracy 0.97)., Conclusion: Fetal nasal bone length at high percentiles in the first trimester of pregnancy may aid in the prediction of adverse outcomes such as preterm labour, preterm premature rupture of membranes and oligohydramnios.

Background: Therapeutic advancements following the introduction of autologous stem cell transplantation and 'novel' agents have significantly improved clinical outcomes for patients with multiple myeloma (MM). Increased life expectancy, however, has led to renewed concerns about the long-term risk of second primary malignancies (SPMs). This review outlines the most up-to-date knowledge of possible host-, disease-, and treatment-related risk factors for the development of SPMs in patients with MM, and provides practical recommendations to assist physicians., Design: A Panel of International Myeloma Working Group members reviewed the most relevant data published in the literature as full papers, or presented at meetings of the American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, or International Myeloma Workshops, up to June 2016. Here, we present the recommendations of the Panel, based on this literature review., Results: Overall, the risk of SPMs in MM is low, multifactorial, and partially related to the length of patients' survival and MM intrinsic susceptibility. Studies suggest a significantly increased incidence of SPMs when lenalidomide is administered either following, or concurrently with, oral melphalan. Increased SPM incidence has also been reported with lenalidomide maintenance following high-dose melphalan, albeit to a lesser degree. In both cases, the risk of death from MM was significantly higher than the risk of death from SPMs, with lenalidomide possibly providing a survival benefit. No increase in SPM incidence was reported with lenalidomide plus dexamethasone (without melphalan), or with bortezomib plus oral melphalan, dexamethasone, or thalidomide., Conclusion: In general, the risk of SPMs should not alter the current therapeutic decision-making process in MM. However, regimens such as lenalidomide plus dexamethasone should be preferred to prolonged exposure to lenalidomide plus oral melphalan. SPM risk should be carefully discussed with the patient in the context of benefits and risks of different treatment options., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Urine culture is the gold standard test for revealing the microbial agent causing urinary tract infection (UTI). Culture results are affected by sampling techniques; improper sampling leads to contamination of urine and thus contamination of the culture with urogenital flora. We aimed to evaluate the effect of urogenital cleansing, performed with chlorhexidine-containing genital region cleansing wipes (GRCW) on contamination rates., Methodology: A total of 2,665 patients with UTI-related complaints and with urine culture requests from various outpatient clinics were enrolled in the study. Of the patients, 1,609 in the experimental group used GRCW before sampling, while 1,046 in the control group did not use any wipes., Results: The contamination rate in the experimental group patients was 7.7%, while it was 15.8% in the control group. Contamination rates were significantly higher in the control group than in the experimental group for both women and men. Contamination rates for children and adults were also significantly lower in the experimental group than in the control group., Conclusions: Our study, conducted in a large population, showed that the use of chlorhexidine-containing cleansing wipes significantly reduced urine culture contamination rates in both genders, in both child and adult age groups. Using GRCW, collection of urine after urogenital area cleansing will decrease the contamination problem.

In this study, associations between IL-4, IL-6, and macrophage migration inhibitory factor (MIF) polymorphisms and susceptibility to brucellosis were investigated. Consecutive adult patients with no known treatment against brucellosis and who did not have any other autoimmune and/or chronic disorders, were included in this study (n = 120, Group I). Age and sex-matched controls who had no other autoimmune and/or chronic disorders were also included (n = 120, healthy volunteers, Group II). The IL4&#95;P2P2 genotype, IL4&#95;P1 allele, and IL4&#95;variable number of tandem repeats (VNTR)&#95;IL6-174CG compound genotype were found to be more frequent in the patient group than in control subjects. There were significant differences between the patients and controls with respect to the frequencies of the IL4&#95;P2P2 genotype (77.5% versus 87.5%; p = 0.001; OR, 0.36; 95% confidence interval [CI], 0.21-0.62) and the IL4&#95;P1 allele (12.1% versus 6.7%; p = 0.030; OR, 0.92; CI, 1.02-3.64). The IL4-VNTR&#95;IL6-174CG compound genotype was also present at a significantly higher frequency in the patient group than in control subjects (11.7% versus 4.2%; p = 0.027, OR, 3.04; CI, 1.06-8.68). No statistically significant differences in the frequencies of the IL-6-174, MIF-173, IL-4&#95;P1P1, and IL4&#95;P2P1 genotypes were observed between patients and control subjects. The IL4&#95;VNTR P1 allele, P2P2 genotypes, and IL4-VNTR&#95;IL6-174CG P2P1-GG genotypes are common in southern Turkey, and carriers of these polymorphisms are susceptible to brucellosis.

Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m 2 (MEL140) was planned. The primary end point was progression-free survival. Of 420 eligible patients, 85% received a first transplant and 69% completed double transplantation. Treatment duration was short with a median of 7.7 months with induction chemotherapy cycles and 4.6 months without induction. On an intention-to-treat basis, median progression-free survival with induction chemotherapy cycles (207 patients) was 21.4 months versus 20.0 months with no induction cycles (213 patients) (hazard ratio 1.04, 95% confidence interval 0.84-1.28; P=0.36). Per protocol, progression-free survival was 23.7 months versus 23.0 months (P=0.28). Patients aged 65 years or over (55%) did not have an inferior outcome. Patients with low-risk cytogenetics [absence of del17p13, t(4;14) and 1q21 gains] showed a favorable overall survival and included the patients with sustained first remission. MEL140 was associated with a low rate of severe mucositis (10%) and treatment-related deaths (1%). Based on hazard ratio, the short treatment arm consisting of mobilization chemotherapy and tandem MEL140 achieved 96% of the progression-free survival, demonstrating its value as an independent component of therapy in older patients with multiple myeloma who are considered fit for autologous transplantation. (clinicaltrials.gov identifier: 02288741)., (Copyright© Ferrata Storti Foundation.)

Background: Although a few case reports about hypertensive anaphylaxis (HA) are available in the present literature, there is no study about the prevalence of HA. In this study, we review our cases with anaphylaxis presenting with hypertension and ascertain its prevalence. The documents of the patients who had anaphylactic reactions after the procedures performed for the diagnosis and treatment of allergic diseases in GATA Haydarpasa Clinic of Allergy and Immunology between January 2010 and December 2014 were retrospectively reviewed. Within the study period, 324 patients had undergone 4332 procedures in which 62 of them had developed anaphylaxis., Results: During the procedures, the rate of anaphylaxis was found to be 1.43 %. The rate of HA among the anaphylaxis patients was 12.9 % (8 of 62 patients). During treatments, 2 patients received adrenaline injections without any adverse reaction., Conclusions: HA may be seen at a considerable rate during an anaphylactic reaction. Anaphylaxis and hypertension can be recovered by adrenaline injection when required. According to the best of our knowledge, this study is the first original study about the prevalence of HA in English-language medical literature.

Objective: Familial Mediterranean Fever (FMF) is an autosomal recessively inherited auto inflammatory disorder. MEFV gene, causing FMF, encodes pyrin that is associated with the interleukin-1 (IL-1) related inflammation cascade. The aim of this study was to investigate the relationship of interleukin-1 receptor antagonist (IL-1Ra) and interleukin-4 (IL-4) polymorphisms with the risk of FMF in the Turkish population., Methods: This study included 160 patients with FMF (74 men, 86 women) and 120 healthy controls (50 men, 70 women), respectively. Genotyping of IL-1Ra rs2234663 polymorphism was evaluated by gel electrophoresis after polymerase chain reaction (PCR). The IL-4 rs79071878 polymorphism was determined by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis. The results of analyses were evaluated for statistical significance., Results: There was no significant difference in IL-1Ra genotype and allele distributions between FMF and the control groups (p>0.05). However, a significant association was observed between FMF patients and control groups according to IL-4 genotype distribution (p=0.016), but no association was found in the allelic frequency of IL-4 between FMF patients and the controls (p>0.05, OR: 1.131, CI 95%: 0.71-1.81)., Conclusions: The IL-4 rs79071878 polymorphism, was associated whereas the IL-1Ra rs2234663 polymorphism was not associated with FMF risk in the Turkish population. Larger studies with different ethnicities are needed to determine the impact of IL-1Ra and IL-4 polymorphism on the risk of developing FMF., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.

Objective: To compare the diagnostic efficacy and agreement of the traditional tuberculin skin test with QuantiFERON-Tuberculosis Gold In-Tube test for latent tuberculosis infection in healthcare workers., Methods: The cross-sectional analytical study was conducted between March 1 and 31, 2008, at a specialist tuberculosis hospital in Istanbul, Turkey, and comprised healthcare workers who had been employed for at least one year at the hospital and volunteered to take part. Tuberculin skin test and QuantiFERON-Tuberculosis Gold In-Tube test were both performed simultaneously and their results were compared Using SPSS 12., Results: Out of 34 subjects, 20(58.8%) had a positive tuberculin skin test, and 7(20.6%) had a positive QuantiFERON-Tuberculosis Gold In-Tube test. The two tests agreed in only 15(44.1%) cases and disagreed in 19(55.9%). In 16(47.1%) subjects, the QuantiFERON-Tuberculosis Gold In-Tube test was negative and tuberculin skin testwas positive, while in 3(8.8%) participants QuantiFERON-Tuberculosis Gold In-Tube test was positive and tuberculin skin test was negative. Kappa test revealed discordance between the two tests (k=-0.13; p=0.92)., Conclusions: Latent tuberculosis infection prevalence was higher based on tuberculin skin test than QuantiFERON-Tuberculosis Gold In-Tube test. The results of the two tests were discordant.