Effect of FADS1 SNPs rs174546, rs174547 and rs174550 on blood fatty acid profiles and plasma free oxylipins.

Introduction: Previous studies have indicated that activity of fatty acid desaturase 1 (FADS1), is involved in cardiometabolic risk. Recent experimental data have shown that FADS1 knockdown can promote lipid accumulation and lipid droplet formation in liver cells. In this study, we aimed to characterize whether different FADS1 genotypes affect liver fat content, essential fatty acid content and free oxylipin mediators in the blood. Methods: We analyzed the impact of FADS1 single-nucleotide polymorphisms (SNPs) rs174546, rs174547, and rs174550 on blood fatty acids and free oxylipins in a cohort of 85 patients from an academic metabolic medicine outpatient center. Patients were grouped based on their genotype into the homozygous major (derived) allele group, the heterozygous allele group, and the homozygous minor (ancestral) allele group. Omega-3 polyunsaturated fatty acids (n-3 PUFA) and omega-6 polyunsaturated fatty acids (n-6 PUFA) in the blood cell and plasma samples were analyzed by gas chromatography. Free Oxylipins in plasma samples were analyzed using HPLC-MS/MS. Liver fat content and fibrosis were evaluated using Fibroscan technology. Results: Patients with the homozygous ancestral (minor) FADS1 genotype exhibited significantly lower blood levels of the n-6 PUFA arachidonic acid (AA), but no significant differences in the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There were no significant differences in liver fat content or arachidonic acid-derived lipid mediators, such as thromboxane B2 (TXB2), although there was a trend toward lower levels in the homozygous ancestral genotype group. Discussion: Our findings suggest that FADS1 genotypes influence the blood levels of n-6 PUFAs, while not significantly affecting the n-3 PUFAs EPA and DHA. The lack of significant differences in liver fat content and arachidonic acid-derived lipid mediators suggests that the genotype-related variations in fatty acid levels may not directly translate to differences in liver fat or inflammatory lipid mediators in this cohort. However, the trend towards lower levels of certain lipid mediators in the homozygous ancestral genotype group warrants further investigation to elucidate the underlying mechanisms of different FADS1 genotypes and potential implications for cardiometabolic risk.

Harnessing Oxylipins and Inflammation Modulation for Prevention and Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, ranking as the third most malignant. The incidence of CRC has been increasing with time, and it is reported that Westernized diet and lifestyle play a significant role in its higher incidence and rapid progression. The intake of high amounts of omega-6 (n - 6) PUFAs and low levels of omega-3 (n - 3) PUFAs has an important role in chronic inflammation and cancer progression, which could be associated with the increase in CRC prevalence. Oxylipins generated from PUFAs are bioactive lipid mediators and have various functions, especially in inflammation and proliferation. Carcinogenesis is often a consequence of chronic inflammation, and evidence has shown the particular involvement of n - 6 PUFA arachidonic acid-derived oxylipins in CRC, which is further described in this review. A deeper understanding of the role and metabolism of PUFAs by their modifying enzymes, their pathways, and the corresponding oxylipins may allow us to identify new approaches to employ oxylipin-associated immunomodulation to enhance immunotherapy in cancer. This paper summarizes oxylipins identified in the context of the initiation, development, and metastasis of CRC. We further explore CRC chemo-prevention strategies that involve oxylipins as potential therapeutics.

Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolite levels, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of cytochrome-P450 (CYP)-derived epoxide metabolites derived from PUFA, such as omega-6 arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding dihydroxy metabolites. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) have shown that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this study, we found a significant increase in EET levels in 43 HCC patients treated with sorafenib and a trend towards increased levels of DHA-derived 19,20-EDP. We demonstrate that the effect of sorafenib on CYP- metabolites led to an increase of 19,20-EDP and its dihydroxy metabolite, whereas DHA plasma levels decreased under sorafenib treatment. These data indicate that specific supplementation with DHA could be used to increase levels of the epoxy compound 19,20-EDP with potential anti-tumor activity in HCC patients receiving sorafenib therapy.

Corrigendum: Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fphar.2023.1124214.].

The Bad Bug is Back: Acinetobacter Baumannii Bacteremia Outbreak during the COVID-19 Pandemic in an Intensive Care Unit.

Background: Epidemiology of nosocomial infections may show variability because of under-estimation of infection control measures (ICMs) in coronavirus disease 19 (COVID-19) outbreak. Aim: To investigate the Acinetobacter bacteremia outbreak developed in an intensive care unit (ICU) between March 20 to May 15, 2020, examine the risk factors, and re-evaluate ICM retrospectively. Material and Methods: A retrospective cohort analysis was conducted to determine the risk factors, pulsed field gel electrophoresis (PFGE) was performed for analysis of the outbreak, ICM practices were observed by a team, and infection control interventions were undertaken. Results: Acinetobacter bacteremia developed in 17 patients (21.5%) within 79 COVID-19 patients included in the study. The mean age of the bacteremic patients was 67.3 (SD = 14.82) years, and 82.4% of them were male; of these, 15 died, leading to 88.2% mortality. The bacteremia rate was higher compared with a 14-month period preceding the COVID-19 pandemic (17/79 versus 12/580 patients, respectively). PFGE revealed that the outbreak was polyclonal. On multi-variate analysis, the bacteremia development rate was 13.7 and 5.06 times higher with central venous catheter (CVC) use and in patients with chronic obstructive pulmonary disease (COPD), respectively. The mortality rate was higher in bacteremic patients (p = 0.0016). It was observed that ICMs were not followed completely, especially change of gloves and hand hygiene. Contamination of A. baumannii was observed in 38% of the gloves. Conclusion: COPD and CVC use were determined as risk factors for Acinetobacter bacteremia development, and failures in ICM may have led to cross-contamination of endemic A. baumannii. The outbreak could be controlled within 3 weeks of interventions.

Emergency response, intervention, and societal recovery in Greece and Turkey after the 30th October 2020, MW = 7.0, Samos (Aegean Sea) earthquake.

On 30 October 2020, an Mw = 7.0 earthquake struck the Eastern Aegean Sea with considerable impact on Samos Island in Greece and the area of Izmir in Turkey. It was the most lethal seismic event in 2020 worldwide, and the largest and most destructive in the Aegean Sea since the 1955 earthquake that also affected both countries. The Civil Protection authorities in Greece and Turkey were effectively mobilized responding to the earthquake emergency. The main response actions comprised initial announcements of the earthquake and first assessment of the impact, provision of civil protection guidelines through emergency communication services, search and rescue operations,medical care, set up of emergency shelters and provisions of essential supplies, psychological support, as well as education, training activities and financial support to the affected population. From the comparison of the Civil Protection framework and the implemented response actions, it is seen that actions at both sides of the eastern Aegean Sea, followed a single-hazard approach in disaster management with similar response activities coordinated by a main Civil Protection agency, which was in close cooperation with the respective authorities at a national, regional and local level. Based on the presented information, it is concluded that the post-earthquake response and emergency management were satisfactory in both countries, with valuable lessons learnt ahead of the next major earthquake. To this end, many aspects can be further addressed to enhance community resilience and introduce a multi-hazard approach in (natural and man-made) disaster management.

Knowledge and attitudes towards oral and dental health among seventh and eighth grade students compared with their teeth examination.

AIM: Oral and dental heath are important aspects of general health and impact the quality of life and well-being. In this study, we aimed to assess the level of knowledge and attitudes towards oral and dental health and to examine the relative effect of social-behavioural risk factors on caries and other teeth problems among seventh and eighth grade students. METHODS: Study Design: The study population consisted of all seventh and eighth graders who started the 2011 school year in Sarigol village of the Manisa city, Turkey (n = 377). Data were gathered by questionnaires which were carried out before tooth examination. Associations between sociodemographic characteristics, knowledge items, attitudinal factors and number of dental caries, dental fillings and teeth loss were studied. RESULTS: Oral health was worse among females (p=0.002). As the number of children under care increased in the house, the number of dental filling and teeth loss increased in the students (p= 0.001 and p=0.021). Education of mothers of students who had worse dental health was significantly lower compared to the others (p=0.029). Among students who had four and more dental caries and dental fillings, frequency of dentist visit was lower (p= 0.034 and p= 0.005). Among students who had more dental caries, the knowledge that consumption of acidic beverages is not good for oral health was less prevalent (p=0.011). STATISTICS: Associations between sociodemographic characteristics, knowledge items, attitudinal factors and number of dental caries, dental fillings and teeth loss were studied using chi-square test. CONCLUSIONS: Health authorities should strengthen the implementation of oral disease prevention and oral health promotion programs rather than traditional curative care. Community-oriented education programs for students and their families are crucial for this purpose.

Assessment of the Effect of Sorafenib on Omega-6 and Omega-3 Epoxyeicosanoid Formation in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death. The multikinase inhibitor sorafenib is widely used for systemic therapy in advanced HCC. Sorafenib might affect epoxyeicosanoids, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of epoxides derived from long-chain polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding diols. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) showed that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this pilot study, we assessed the effect of sorafenib treatment on the presence of lipid mediators, such as EETs, in blood of the patients with HCC using the lipidomics technology. We found a significant increase in 11,12-EET and 14,15-EET levels in HCC patients treated with sorafenib. Furthermore, while not significant in this small sample set, the data presented indicate that sorafenib can also increase the level of omega-3 DHA-derived 19,20-EDP. While the effect on EETs might hamper the anti-tumor effect of sorafenib, we hypothesize that supplementation of DHA in sorafenib-treated HCC patients could increase the level of 19,20-EDP and thereby enhance its anti-tumor effect.

Comparison of mental health, quality of sleep and life among patients with different stages of chronic kidney disease and undergoing different renal replacement therapies.

BACKGROUND: The present study aimed to investigate and compare mental health, health-related quality of life, and sleep levels of patients with various stages of chronic kidney disease (CKD) and undergoing different renal replacement therapies and analyze the factors affecting these parameters. METHODS: Overall, 140 patients with a mean age of 43 ± 14 years were recruited into this study. Study groups [controls and patients with CKD undergoing predialysis, hemodialysis (HD), peritoneal dialysis, kidney transplantation (KT)] were evaluated using Short Form Health Survey-36 (SF-36), Kidney Disease Quality of Life-36 (KDQoL-36), Pittsburgh Sleep Quality Index (PSQI), and General Health Questionnaire-12 (GHQ-12). RESULTS: The KT group had the highest scores in physical and mental components of the subscales of SF-36 and KDQoL-36 but the lowest scores in PSQI and GHQ-12, indicating the best results in terms of mental health and quality of life, and sleep. Serum albumin and hemoglobin levels were positively correlated with several subscales of quality of life. Significant negative correlations were observed among PSQI, GHQ-12, and subscale scores of SF-36 and KDQoL-36. The HD group showed significantly lower scores in the subscales of symptoms and burden of kidney disease of KDQoL-36. CONCLUSION: KDQoL was worse in the HD group and better in the KT group than in other groups. Serum albumin and hemoglobin levels, and Kt/V (dialyzer clearance of urea multiplied by dialysis time and normalized for urea distribution volume ) values of patients with CKD exerted a linear and significant effect on the quality of life, which showed a significant positive correlation with the quality of sleep and mental health. In contrast, serum calcium x phosphorus levels showed an inverse correlation with the subscale scores of KDQoL. HIPPOKRATIA 2020, 24(2): 51-58.

Disease activity, handgrip strengths, and hand dexterity in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the hand joints and leading to impairment in hand functions. Evaluation of functional impairment is necessary for assessing patient's quality of life, disease activity, and treatment outcome. To date, many scientific studies assessed the disease activity of patients with RA, but little attention has been carried out to assess these patients' hand functions and dexterity. The purposes of this study were to determine the clinical relevance of the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), hand dexterity with the Purdue Pegboard Test (PPT), and handgrip strength and pinch strengths of RA patients and to look into their relation between each other. A prospective trial was performed in women with RA who were followed at the physical medicine and rehabilitation department of our university hospital. Eighty-two women between the ages of 18 and 70, with a diagnosis of RA according to the 2010 American College of Rheumatology/the European League Against Rheumatism (ACR/EULAR) criterion, were recruited to the study. The Disease Activity Scores were determined by using Disease Activity Score-28 (DAS-28). Handgrip strength was measured with a Jamar dynamometer, and lateral, palmar, and tip pinch strengths were measured by a pinchmeter. Hand functions were evaluated with the PPT, and functional outcomes were assessed with the QuickDASH questionnaire. The mean age of the study group was 49.27 ± 10.69 years. The average values of DAS-28 and the QuickDASH values were found to be 4.22 ± 1.28 and 38.33 ± 19.78, consecutively. High correlation was observed between DAS-28 and the QuickDASH values (p < 0.001). The mean grip strengths in both hands were significantly correlated with the QuickDASH values (p < 0.001), and also, DAS-28 values were very significantly correlated with the mean grip strength in the dominant hand (p < 0.001) and in the nondominant hand (p < 0.01). The mean lateral pinch strengths in both hands were correlated statistically significantly with DAS-28 and the QuickDASH scores (p < 0.001). The mean tip pinch strengths in both hands were correlated with DAS-28 scores, but correlation with the QuickDASH scores was seen just in the dominant hand (p < 0.05). There was no correlation between palmar pinch strengths in both hands with the DAS-28 and QuickDASH scores (p > 0.05). DAS-28 was correlated with PPT performance on the dominant hand (p < 0.05), but there was no correlation with the nondominant hand, both hands, and assembly (p > 0.05). The QuickDASH values were not correlated with all PPT performances (p > 0.05). Handgrip strengths of both hands were positively correlated with the PPT performances (p < 0.05). In conclusion, we determined that handgrip strengths were significantly related to disability and disease activity in the RA patients in our study. The QuickDASH is practical to use in clinical practice, and positively correlates with the disease activity. Dexterity measurements with PPT in the RA patient group were found practical and effective in our study. As a result, we can suggest using QuickDASH questionnaire for functional outcomes, handgrip strength measurements for assessment of hand disability and functional impairments, and also dexterity measurements even in patients with low disease activity.

A novel graft option after pterygium excision: platelet-rich fibrin for conjunctivoplasty.

PurposeTo compare the surgical results, complications, and recurrence rates of primary pterygium excision with conjunctival autografts (CA) vs platelet-rich fibrin (PRF) grafts.Patients and methodsA total of 35 eyes of 35 patients with primary pterygium were included in the study. The patients underwent excision of pterygium followed by closure of the bare sclera by CA (group 1, n=20) vs PRF grafts (group 2, n=15). The PRF was generated from the patients' own whole-blood sample by centrifugation and pressing. The surgery times, intra/postoperative complications, recurrence rates of pterygium, and changes in visual acuity (VA) were evaluated and compared within groups.ResultsThe mean follow-up period was 14.3±6.5 months (6-24 months). The mean preoperative and postoperative VAs were same (20/25) (P=0.204). The mean surgery time was shorter in group 2 (22.1±1.9 min) compared to group 1 (33.8±7.8 min) (P=0.001). The recurrence was observed only in one (6.6%) case of group 2, while none of the cases showed recurrence in group 1. Graft loss was observed in 2 (10%) cases in group 1, and 1 (6.6%) case in group 2. No other intra/postoperative complications such as tear in the graft, excessive bleeding, scleral necrosis, graft necrosis, pannus formation, or symblepharon occurred in both groups.ConclusionsThis preliminary study showed encouraging results of the application of PRF for conjuntivoplasty after pterygium excision. The use of PRF in pterygium surgery is a simple, easily applicable, and a promising method with low rates of recurrence and complications.

The SWI/SNF Protein PBRM1 Restrains VHL-Loss-Driven Clear Cell Renal Cell Carcinoma.

PBRM1 is the second most commonly mutated gene after VHL in clear cell renal cell carcinoma (ccRCC). However, the biological consequences of PBRM1 mutations for kidney tumorigenesis are unknown. Here, we find that kidney-specific deletion of Vhl and Pbrm1, but not either gene alone, results in bilateral, multifocal, transplantable clear cell kidney cancers. PBRM1 loss amplified the transcriptional outputs of HIF1 and STAT3 incurred by Vhl deficiency. Analysis of mouse and human ccRCC revealed convergence on mTOR activation, representing the third driver event after genetic inactivation of VHL and PBRM1. Our study reports a physiological preclinical ccRCC mouse model that recapitulates somatic mutations in human ccRCC and provides mechanistic and therapeutic insights into PBRM1 mutated subtypes of human ccRCC.

The opinions of adults about the ban on cigarette sales to minors.

BACKGROUND: Selling of tobacco products to minors has been banned since 1996 by the tobacco control law in Turkey. However, it is also important for the public to support practices that prevent the access of tobacco products to minors. In addition, every individual has the responsibility of carrying out society based programs that restrict access to tobacco products especially to children and the youths. Social sensitivity is considered an important factor in the prevention of tobacco use. This study aims to learn about the opinions and attitudes of adults with regards to minors access to tobacco products. METHODS: The study was a descriptive study conducted in nine city centers in Turkey. The total number of participants reached was 3241. The questionnaire was developed by the research team and consisted of 22 questions concerning knowledge and behaviors of adults on restriction of tobacco sales to minors and their observations with regards tobacco sales to minors. Data was collected through face to face interview. Pearson chi-square test was used for the bivariate analysis whereas logistic regression was investigate the relationship between "the participant's response against tobacco sales to minors" and the following explanatory variables; "age", "educational status", "income level", "working status", "minors access to cigarettes", "smoking ratio in high school" and "sales of tobacco to minors". RESULTS: More than half of the participants (60.5%) belonged to the age group 25-44 years, 61.3% graduated from high school or university. Most of the participants were smoker (39.2%) or ex-smoker (19.1%), and 41.7% of the participants was non-smoker. A greater proportion of the participants (76.2%) believed that smoking prevalence was greater than 40% among high school students. One in four (27.8%) adults did not know that tobacco control law bans sell of tobacco products to minors in Turkey. More than half of the participants (57.1%) ever witnessed tobacco sales to minors and 63.6% of them did not act when confronted with the event. Almost all (96.8%) of the respondents thought that access of minors to tobacco products was not difficult. The results of logistic regression of participant's response against tobacco sales to minor and related factors for current smokers showed that respondents who believed smoking ratio in high school was 4-5 adolescent out of 10 (aOR: 1.59; 95% CI: 1.09-2.34) were more likely to give a warning or informing the police or other people as compared to respondents whose perception on the smoking ratio among high school students was 6-7 adolescents out of 10. The results of logistic regression of non-smokers' response against tobacco sales to minor were who are from higher educational level, higher economic status, working status and who believed smoking ratio in high school was 4-5 adolescent out of 10 and 2-3 adolescent out of 10 were more likely to give a warning or informing the police or other people as compared to the others. CONCLUSIONS: Although laws prohibiting the sale of tobacco products to the under age group is very important with regards to accessibility of minors to tobacco products, most of the study participants believed that minors can still easily access tobacco products, and more than half of the participants did not act when confronted with the event. The education, information and monitoring program most especially as it concerns salesman, should be reviewed and strengthened to obey the rules on sales of tobacco products to minors. Education program should be carried out to increase the knowledge and awareness of the community for sale of tobacco to minors. Social sensitivity is important for the prevention of tobacco use and every individual have a responsibility in carrying out this society based program, most especially as it related to prevention of tobacco usage among children and youths.

Mechanistically distinct cancer-associated mTOR activation clusters predict sensitivity to rapamycin.

Genomic studies have linked mTORC1 pathway-activating mutations with exceptional response to treatment with allosteric inhibitors of mTORC1 called rapalogs. Rapalogs are approved for selected cancer types, including kidney and breast cancers. Here, we used sequencing data from 22 human kidney cancer cases to identify the activating mechanisms conferred by mTOR mutations observed in human cancers and advance precision therapeutics. mTOR mutations that clustered in focal adhesion kinase targeting domain (FAT) and kinase domains enhanced mTORC1 kinase activity, decreased nutrient reliance, and increased cell size. We identified 3 distinct mechanisms of hyperactivation, including reduced binding to DEP domain-containing MTOR-interacting protein (DEPTOR), resistance to regulatory associated protein of mTOR-mediated (RAPTOR-mediated) suppression, and altered kinase kinetics. Of the 28 mTOR double mutants, activating mutations could be divided into 6 complementation groups, resulting in synergistic Rag- and Ras homolog enriched in brain-independent (RHEB-independent) mTORC1 activation. mTOR mutants were resistant to DNA damage-inducible transcript 1-mediated (REDD1-mediated) inhibition, confirming that activating mutations can bypass the negative feedback pathway formed between HIF1 and mTORC1 in the absence of von Hippel-Lindau (VHL) tumor suppressor expression. Moreover, VHL-deficient cells that expressed activating mTOR mutants grew tumors that were sensitive to rapamycin treatment. These data may explain the high incidence of mTOR mutations observed in clear cell kidney cancer, where VHL loss and HIF activation is pathognomonic. Our study provides mechanistic and therapeutic insights concerning mTOR mutations in human diseases.

Polymorphisms in the IL28B gene (rs12979860, rs8099917) and the virological response to pegylated interferon therapy in hepatitis D virus patients.

AIM: Few data are available regarding the effects of interleukin 28B (IL28B) polymorphisms in chronic hepatitis D (CHD) patients. This study investigated the relationship between IL28B poly-morphisms and the response of patients with CHD infections to pegylated interferon (PEG-IFN) therapy. MATERIALS AND METHODS: A total of 101 CHD patients were -selected, 80 of whom (46 males ; median age 41 years) satisfied the inclusion criteria and were enrolled in the study. Thirty-seven patients were treated with peg-IFNα for at least 12 months and were followed for a median of 18 months (range, 12-30 months). The primary treatment endpoint was the suppression of HDV replication, as documented by the loss of detectable HDV RNA in serum. Genotyping was used to analyse the IL28B polymorphisms rs12979860 and rs8099917 according to the virological response. RESULTS: After treatment, a sustained viral response (SVR) was achieved in 19 (51%) of the patients treated with PEG-INF. The IL28B genotypes in the 80 patients were as follows : CC in 36 (45%), CT in 33 (41%) and TT in 11 (14%) for rs12979860, and GG in 4 (5%), GT in 27 (34%) and TT in 49 (61%) for rs8099917. SVR was achieved in 5 (26%), 10 (53%) and 4 (21%) patients with CC, CT and TT at rs12979860, respectively, and one (5%), nine (47%) and nine (47%) patients with GG, GT and TT at rs8099917, respectively. There were differences in the SVR among genotypes (rs12979860 and rs8099917 ; chi-squared test, p = 0.047). CONCLUSION: IL28B predicts the PEG-IFN response in patients with CHD infection.

Risk factors for malignancy in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with multisystem involvement. An increased incidence of cancer in SSc patients compared with the general population has been reported in several reports. Our aims in this study were to determine the most common malignancies and to investigate the possible risk factors for the development of malignancy in patients with SSc. Three hundred forty SSc patients from 13 centers were included to the study. Data of the patients were obtained by evaluating their medical records retrospectively. A total of 340 patients with SSc were evaluated. Twenty-five of the patients had 19 different types of malignancy. Bladder cancer was the most common type of cancer with four patients and was followed by breast cancer with three patients, and cervix cancer and ovarian cancer with two patients each. Other types of cancers such as squamous cell skin cancer, adenocancer with an unknown origin, multiple myeloma, chronic myeloid leukemia, papillary thyroid cancer, larynx cancer, non-small cell lung cancer, follicular type non-Hodgkin lymphoma (NHL), endometrium cancer, colon cancer, uterus cancer, neuroendocrine tumor, glioblastoma multiforme, and soft tissue sarcoma were diagnosed in one patient each. The only cancer type that showed an association with cyclophosphamide dose was bladder carcinoma. Other malignancies did not show a correlation with age, sex, smoking, type and duration of the disease, autoantibodies, organ involvement, and dose and duration of cyclophosphamide therapy. Cancer may develop in any organ in patients with SSc. Continuous screening of the patients during a follow-up period is necessary for the early detection of the tumor development.

Comparison of colorectal neoplastic polyps and adenocarcinoma with regard to NLR and PLR.

OBJECTIVE: Cancer-related inflammation affects many aspects of malignancy, including proliferation and survival of malignant cells, angiogenesis, and therapeutic response. Some biomarkers representing the degree of systemic inflammation, such as the Glasgow prognostic score, NLR and PLR, have been shown to have prognostic value in many kinds of cancer patients. Aim of this study to investigate to compare neutrophil/leukocyte (NLR) and platelet/lymphocyte (PLR) ratios of the patients with colorectal neoplastic polyps and colorectal cancer (CRC) and tried to determine whether this could be used as a biomarker in follow up of the patients with neoplastic polyps. PATIENTS AND METHODS: A total of 100 colorectal polyps, 113 colorectal cancers and 124 healthy controls were included in the study. Exculusion criteria were endocrinologic or metabolic diseases, acute or chronic diseases, hypertension and atherosclerotic heart diseases, renal diseases. Blood count parameters of the patients were measured. The NLR was calculated as a simple ratio between the absolute neutrophil and the absolute lymphocyte counts. The PLR was defined as the platelet counts to lymphocyte ratio. RESULTS: A statistically significant difference was not detected between Group A and C with regard to NLR and PLR. NLR and PLR were found statistically significantly high in Group B (CRC), Group A (colorectal polyp) and Group C (healthy individuals) (p < 0.001 and p < 0.001). Our study showed that the optimum NLR cut-off point for neoplastic polyps was 2.28 (sensitivity: 68.7%, specificity: 42.3%). When the sensitivity and specificity levels of the PLR were assessed, they were 68.7% and 46.5% for neoplastic polyps, 80% and 68.9% for colorectal cancer. CONCLUSIONS: NLR and PLR may be used for follow up conversion of colonic and rectal neoplastic polyps to invasive tumor.

The influence of the learning effect on automated perimetry in a Turkish population.

PURPOSE: To evaluate the influence of learning effect on the outcome of automated perimetry and to assess the factors associated with the learning effect in a Turkish population. METHODS: The Swedish Interactive Threshold Algorithm (SITA) standard 30-2 test was performed on a Humphrey Visual Field Analyzer in 102 normal Turkish subjects who had not previously undertaken any form of perimetry. Each subject completed three testing sessions, each separated by at least one day. The SITA standard 30-2 testing sessions included both eyes. The right eye was always tested before left eye. The reliability parameters, test duration and visual field (VF) global indices (mean deviation [MD] and pattern standard deviation [PSD]) obtained from right eyes in the first and third sessions were compared to assess the learning effect. Change in these parameters between the first and third sessions was calculated, and the effect of gender, age and educational level on this change was evaluated. RESULTS: The reliability parameters, test duration and VF global indices each improved between the first and third sessions (P ≤ 0.001). The change in the parameters was greater in subjects over 50 years of age and with an educational level less than high school (P ≤ 0.01). No correlation was found between learning effect and gender. CONCLUSION: In normal Turkish subjects, a significant learning effect was observed during VF testing with the SITA standard 30-2. The learning effect was correlated with age and educational level.

Low "quotient" Lp(a) concentration mediates autoimmune activation and independently predicts cardiometabolic risk.

OBJECTIVE: We determined whether U-shaped relationships exist between serum lipoprotein[Lp](a) and cardiometabolic risk. METHODS: In population-based nondiabetic and diabetic middle-aged adults (n=1 428 and 241, respectively) who had been genotyped for the LPA rs10455872 A>G polymorphism, we adjusted the Lp(a) concentration for the effects of genotype and other covariates. Via sex-specific equations we estimated expected Lp(a) concentration in each participant, and the quotient between observed to expected Lp(a) values was determined. Lp(a) and Lp(a) quotient tertiles served to identify non-linear associations with outcomes. RESULTS: Incident 81 cases of diabetes and 128 of coronary heart disease (CHD) developed at 5.1 years' follow-up. Lp(a) concentration was linearly associated with the LPA genotype, gender, total cholesterol, (inversely) fasting insulin, which together with age formed the variables to derive the equations. In logistic regression for incident diabetes, the low Lp(a) quotient tertile was a predictor (RR 1.95 [95%CI 1.10; 3.47]) alike the low Lp(a) tertile, additively to major confounders. Cox regression models comprising sex, age, LPA genotype, smoking status, systolic pressure and serum HDL-cholesterol disclosed that, compared with the mid-tertile, both low (HR 1.77) and high Lp(a) quotient tertiles significantly predicted incident CHD, especially in women. CONCLUSION: Elevated cardiometabolic risk is conferred by apparently reduced circulating Lp(a) assays supporting the notion that "low" serum Lp(a), mediating autoimmune activation, is a major determinant of cardiometabolic risk.

Proteasome inhibitors evoke latent tumor suppression programs in pro-B MLL leukemias through MLL-AF4.

Chromosomal translocations disrupting MLL generate MLL-fusion proteins that induce aggressive leukemias. Unexpectedly, MLL-fusion proteins are rarely observed at high levels, suggesting excessive MLL-fusions may be incompatible with a malignant phenotype. Here, we used clinical proteasome inhibitors, bortezomib and carfilzomib, to reduce the turnover of endogenous MLL-fusions and discovered that accumulated MLL-fusions induce latent, context-dependent tumor suppression programs. Specifically, in MLL pro-B lymphoid, but not myeloid, leukemias, proteasome inhibition triggers apoptosis and cell cycle arrest involving activation cleavage of BID by caspase-8 and upregulation of p27, respectively. Furthermore, proteasome inhibition conferred preliminary benefit to patients with MLL-AF4 leukemia. Hence, feasible strategies to treat cancer-type and oncogene-specific cancers can be improvised through harnessing inherent tumor suppression properties of individual oncogenic fusions.