The Most Predictive Red Flags for Suspecting Cardiac Amyloidosis in Patients with Heart Failure with Preserved Ejection Fraction.

OBJECTIVE: Cardiac amyloidosis (CA) is a cardiomyopathy characterized by amyloid infiltration in the myocardium. Transthyretin cardiac amyloidosis (TTR-CA), commonly presenting as heart failure with preserved ejection fraction (HFpEF), was the focus of our study, which aimed to identify red flags that heighten suspicion of CA in HFpEF patients. METHODS: We prospectively included patients diagnosed with HFpEF. All patients were assessed for TTR-CA red flag features, cardiac and extra-cardiac, as outlined in the 'Diagnosis and Treatment of Cardiac Amyloidosis: A Position Statement of the European Society of Cardiology.' Technetium-99m pyrophosphate (99mTc-PYP) cardiac scintigraphy was performed in 167 HFpEF patients suspected of having TTR-CA. Patients testing positive and negative for TTR-CA were compared based on these red flag features. RESULTS: Out of 167 HFpEF patients, 19 (11.3%) were diagnosed with TTR-CA. In the TTR-CA group, 17 (89.5%) patients were 65 years or older. The presence of three or more red flags differentiated the TTR-CA positive and negative groups (P = 0.040). Features such as low voltage and pseudo infarct patterns were more prevalent in the TTR-CA group (P < 0.001 and P < 0.048, respectively). Left ventricular global longitudinal strain (LV-GLS) was lower in the TTR-CA positive group (P < 0.001). Multivariate analysis identified four variables-older age, pseudo infarct pattern, low/decreased QRS voltage, and LV-GLS-as strong, independent predictors of TTR-CA, with significant odds ratios (ORs) of 7.8, 6.8, 16.9, and 1.2, respectively. CONCLUSION: In this study, TTR-CA etiology occurs in approximately one in every ten HFpEF patients. The presence of three or more red flags increases the likelihood of TTR-CA. Older age, pseudo infarct pattern, low/decreased QRS voltage, and reduced LV-GLS are the most significant red flags indicating TTR-CA in HFpEF patients.

Effect of Humor on Pain and Anxiety in Patients With Rheumatoid Arthritis: A Prospective, Randomized Controlled Study.

Humor can contribute to nursing practices for relieving pain and anxiety in patients with rheumatoid arthritis (RA) during intravenous (IV) biologic treatment. This study used a prospective, randomized controlled study design to investigate the effect of humor on pain and state anxiety in patients with RA receiving IV infusion therapy. Two sample groups were formed: the intervention group (watching a comedy movie) (n = 18) and the control group (usual care) (n = 18). Both groups received IV biologic therapy. A significant difference was found between the groups' pain mean scores, but the effect size was small (P < .001, η² = 0.032). The mean visual analog scale scores decreased in both groups after the treatment; however, it decreased more in the intervention group (P < .001, Md = 2.44) than in the control group (P = .017, Md = 0.83). No significant difference was found between the groups' mean state anxiety scores, and the effect size was irrelevant (P > .05, η² = 0.001). There was a significant decrease in the anxiety levels of both groups (P < .001). During IV biologic infusion therapy, watching comedy movies is recommended as a nursing care intervention for reducing pain in patients with RA in cooperation with other health professionals.

Effect of dual-task training on balance in older adults: A systematic review and meta-analysis.

PURPOSE: Our review aims to analyze the effect of dual-task training (DTT) on balance in healthy older adults. METHODS: PubMed, EbscoHost, Web of Science (WOS), Scopus, Cochrane Library, MEDLINE, EBSCO Open Dissertations, ULAKBIM (TR Index) and YOK (Council of Higher Education Thesis Center) databases and the gray literature were searched. The quality of the studies was assessed with the Cochrane Risk of Bias tool and statistical analysis of the data was performed with Comprehensive Meta-Analysis (CMA) software. A funnel plot and Egger's test were used to detect publication bias. Fourteen studies with 691 participants were included. RESULTS: According to the results of our study, DTT was found to have a significant benefit on balance in older adults than the non-intervention group (standardized mean difference (SMD): -0.691: -1.153, -0.229, 95 % confidence interval (CI)). Furthermore, DTT was superior to different intervention groups in improving balance in older adults (SMD: -0.229: -0.441, -0.016, 95 % CI). CONCLUSION: The findings of this review suggest that DTT may be an effective intervention to improve balance in healthy older adults.

Performance analysis of pretrained convolutional neural network models for ophthalmological disease classification / Análise de desempenho de modelos de rede neural convolucional pré-treinados para classificação de doenças oftalmológicas

ABSTRACT Purpose: This study aimed to evaluate the classification performance of pretrained convolutional neural network models or architectures using fundus image dataset containing eight disease labels. Methods: A publicly available ocular disease intelligent recognition database has been used for the diagnosis of eight diseases. This ocular disease intelligent recognition database has a total of 10,000 fundus images from both eyes of 5,000 patients for the following eight diseases: healthy, diabetic retinopathy, glaucoma, cataract, age-related macular degeneration, hypertension, myopia, and others. Ocular disease classification performances were investigated by constructing three pretrained convolutional neural network architectures including VGG16, Inceptionv3, and ResNet50 models with adaptive moment optimizer. These models were implemented in Google Colab, which made the task straight-forward without spending hours installing the environment and supporting libraries. To evaluate the effectiveness of the models, the dataset was divided into 70%, 10%, and 20% for training, validation, and testing, respectively. For each classification, the training images were augmented to 10,000 fundus images. Results: ResNet50 achieved an accuracy of 97.1%; sensitivity, 78.5%; specificity, 98.5%; and precision, 79.7%, and had the best area under the curve and final score to classify cataract (area under the curve = 0.964, final score = 0.903). By contrast, VGG16 achieved an accuracy of 96.2%; sensitivity, 56.9%; specificity, 99.2%; precision, 84.1%; area under the curve, 0.949; and final score, 0.857. Conclusions: These results demonstrate the ability of the pretrained convolutional neural network architectures to identify ophthalmological diseases from fundus images. ResNet50 can be a good architecture to solve problems in disease detection and classification of glaucoma, cataract, hypertension, and myopia; Inceptionv3 for age-related macular degeneration, and other disease; and VGG16 for normal and diabetic retinopathy.

RESUMO Objetivo: Avaliar o desempenho de classificação de modelos ou arquiteturas de rede neural convolucional pré--treinadas usando um conjunto de dados de imagem de fundo de olho contendo oito rótulos de doenças diferentes. Métodos: Neste artigo, o conjunto de dados de reconhecimento inteligente de doenças oculares publicamente disponível foi usado para o diagnóstico de oito rótulos de doenças diferentes. O banco de dados de reconhecimento inteligente de doenças oculares tem um total de 10.000 imagens de fundo de olho de ambos os olhos de 5.000 pacientes para oito categorias que contêm rótulos saudáveis, retinopatia diabética, glaucoma, catarata, degeneração macular relacionada à idade, hipertensão, miopia, outros. Investigamos o desempenho da classificação de doenças oculares construindo três arquiteturas de rede neural convolucional pré-treinadas diferentes, incluindo os modelos VGG16, Inceptionv3 e ResNet50 com otimizador de Momento Adaptativo. Esses modelos foram implementados no Google Colab o que facilitou a tarefa sem gastar horas instalando o ambiente e suportando bibliotecas. Para avaliar a eficácia dos modelos, o conjunto de dados é dividido em 70% para treinamento, 10% para validação e os 20% restantes utilizados para teste. As imagens de treinamento foram expandidas para 10.000 imagens de fundo de olho para cada tal. Resultados: Observou-se que o modelo ResNet50 alcançou acurácia de 97,1%, sensibilidade de 78,5%, especificidade de 98,5% e precisão de 79,7% e teve a melhor área sob a curva e pontuação final para classificar a categoria da catarata (área sob a curva=0,964, final=0,903). Em contraste, o modelo VGG16 alcançou uma precisão de 96,2%, sensibilidade de 56,9%, especificidade de 99,2% e precisão de 84,1%, área sob a curva 0,949 e pontuação final de 0,857. Conclusão: Esses resultados demonstram a capacidade das arquiteturas de rede neural convolucional pré-treinadas em identificar doenças oftalmológicas a partir de imagens de fundo de olho. ResNet50 pode ser uma boa solução para resolver problemas na detecção e classificação de doenças como glaucoma, catarata, hipertensão e miopia; Inceptionv3 para degeneração macular relacionada à idade e outras doenças; e VGG16 para retinopatia normal e diabética.

Pre-Procedural Right Atrial Diameter May Predict the Development of Typical Atrial Flutter in Patients Undergoing Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Some patients undergoing catheter ablation for atrial fibrillation may develop typical atrial flutter on follow-up, and a second procedure for typical atrial flutter is often required in such patients. In this study, we aimed to define the variables associated with the development of typical atrial flutter after ablation. METHODS: One hundred fifty-nine patients who underwent catheter ablation for the first time due to atrial fibrillation and who did not have a previously documented atrial flutter were included in the study. Before ablation, baseline clinical features and echocardiographic parameters were recorded. At the 1st, 3rd, 6th, and 12th months after the procedure, and then annually, the patients were followed up for typical atrial flutter development. RESULTS: At a mean follow-up of 34.0 (14.0-50.0) months, typical atrial flutter developed in 21 (13.2%) patients. During the follow-up, right atrial diameter was greater in those who developed typical atrial flutter than those who did not [39.0 (38.0-43.0) vs. 36.0 (34.0-39.0) mm, P <.001]. A multiple Cox regression analysis showed that the right atrial diameter was the only independent predictor of typical atrial flutter development (hazard ratio = 1.12, 95% CI: 1.02-1.23, P =.021). A receiver operating characteristic analysis showed that the best cutoff for the right atrial diameter was 38.5 mm to predict typical atrial flutter development (area under the curve = 0.77, 95% CI: 0.67-0.86, sensitivity = 62%, specificity = 75%, P <.001). CONCLUSION: In patients undergoing catheter ablation for atrial fibrillation, a pre-procedural right atrial diameter measurement may predict typical atrial flutter development at follow-up. In particular, patients with a pre-procedural right atrial diameter ≥39 mm may be at a higher risk for developing typical atrial flutter in the future.

Significance of High-Mobility Group A Protein 2 Expression in Pancreatic Ductal Adenocarcinoma and Ampullary Adenocarcinoma.

BACKGROUND/AIMS: Pancreatic and ampullary adenocarcinoma (AAC) are quite resistant to chemotherapy with high metastasis potential. Our study aimed to interpret high-mobility group A protein 2 (HMGA2) expression in benign and precursor pancreatic lesions and pancreatic and ampullary carcinoma and to evaluate its relationship with epithelial-mesenchymal transition (EMT) and clinicopathological parameters. MATERIALS AND METHODS: In this study, normal-appearing pancreas, chronic pancreatitis (CP), low- (L) and high (H)-grade pancreatic intraepithelial neoplasia (PanIN), pancreatic ductal adenocarcinoma (PDAC), and AAC were evaluated with the immunohistochemical marker of HMGA2. Vimentin and E-cadherin immunohistochemical stains were applied in PDAC and AAC. RESULTS: The HMGA2 expression was not detected in normal-appearing pancreas, CP, and L-PanIN. A statistically significant expression was observed in PDAC and H-PanIN (P < .001). A statistically significant correlation was found between loss of membranous E-cadherin expression and vimentin positivity and HMGA2 expression (P > .05). The HMGA2 expression was observed to increase the risk of diseaserelated death and decrease overall survival (OS) in AAC and the neoplasia group (P = .002 and P = .016, respectively). There was no significant difference in OS and risk of death in PDAC (P > .05) with respect to HMGA2 positivity. CONCLUSION: High-mobility group A protein 2 is a helpful immunohistochemical marker in differentiating CP from PDAC. It also plays a role in EMT and may serve as a potential new prognostic agent and therapeutic target in tumors of the periampullary region, especially AAC.

HLA Alleles, Genotype and Haplotype Analyzes from Central Anatolia Region of Turkey

Background: Although human leukocyte antigen (HLA) data for the Turkish population has been reported, there are no statistics on the HLA-DPB1 locus, which has recently received significant attention, particularly in hematopoietic stem cell transplantation. In addition, there is no study that has reported the 2-6 loci HLA haplotype distribution, 8-digit HLA allele frequency, and genotype frequency in the Turkish population. Aims: To evaluate the low and high resolution (2-4-8 digits) HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 allele data using the data of 6100 healthy individuals from the Central Anatolian region of Turkey. Study Design: Retrospective cross-sectional study. Methods: All tests were performed using molecular HLA techniques: low-resolution DNA-based sequence-specific oligonucleotides, low/high-resolution DNA-based sequence-specific primer, and high-resolution next generation sequencing. A total of 6100 healthy donors with a minimum of 3 loci (HLA-A, -B, -DRB1) were analyzed for their HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 data. Pypop and HLA-net GENE[RATE] were used to analyze the data. Results: Among the HLA class I alleles, the following were the most frequently observed alleles: for HLA-A, A*02, A*24, A*03, and A*01; for HLA-B, B*35, B*51, and B*44; and for HLA-C, C*07, C*04, and C*12. Among the HLA class II alleles, the following alelles were the most frequently observed: for HLA-DRB1, DRB1*11, DRB1*04, and DRB1*13; for HLA-DQB1, DQB1*03, DQB1*05, and DQB1*06; and for HLA- DPB1, DPB1*04, DPB1*02, and DPB1*03. The most common alleles among HLA-DPB1 in the 4-digit evaluation were DPB1*04:01, DPB1*02:01, and DPB1*04:02. Among the HLA classes I and II, the following were the most frequently observed 8-digit alleles in HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 were A*02:01:01:01, B*49:01:01:01, C*04:01:01:06, DRB1*07:01:01:01, DQB1*03:01:01:02, and DPB1*02:01:02:05, respectively. The most common 6 loci haplotype was A*02~B*35~C*04~DRB1*11~DQB1*03~DPB1*04 (2.71%). Conclusion: In this study, low and high resolution HLA-DPB1 allele frequency, 6 locus haplotype frequency and genotype frequency were reported for the first time in Turkish population. These new data can be used to map HLA in our country and may provide ideas for potential future studies.

Performance analysis of pretrained convolutional neural network models for ophthalmological disease classification.

PURPOSE: This study aimed to evaluate the classification performance of pretrained convolutional neural network models or architectures using fundus image dataset containing eight disease labels. METHODS: A publicly available ocular disease intelligent recognition database has been used for the diagnosis of eight diseases. This ocular disease intelligent recognition database has a total of 10,000 fundus images from both eyes of 5,000 patients for the following eight diseases: healthy, diabetic retinopathy, glaucoma, cataract, age-related macular degeneration, hypertension, myopia, and others. Ocular disease classification performances were investigated by constructing three pretrained convolutional neural network architectures including VGG16, Inceptionv3, and ResNet50 models with adaptive moment optimizer. These models were implemented in Google Colab, which made the task straight-forward without spending hours installing the environment and supporting libraries. To evaluate the effectiveness of the models, the dataset was divided into 70%, 10%, and 20% for training, validation, and testing, respectively. For each classification, the training images were augmented to 10,000 fundus images. RESULTS: ResNet50 achieved an accuracy of 97.1%; sensitivity, 78.5%; specificity, 98.5%; and precision, 79.7%, and had the best area under the curve and final score to classify cataract (area under the curve = 0.964, final score = 0.903). By contrast, VGG16 achieved an accuracy of 96.2%; sensitivity, 56.9%; specificity, 99.2%; precision, 84.1%; area under the curve, 0.949; and final score, 0.857. CONCLUSIONS: These results demonstrate the ability of the pretrained convolutional neural network architectures to identify ophthalmological diseases from fundus images. ResNet50 can be a good architecture to solve problems in disease detection and classification of glaucoma, cataract, hypertension, and myopia; Inceptionv3 for age-related macular degeneration, and other disease; and VGG16 for normal and diabetic retinopathy.

The Effect of Antioxidant Astaxanthin on Intestinal Ischemia Reperfusion Damage in Rats.

BACKGROUND: Mesenteric ischemia is a frequently encountered disease in surgical clinics, difficult to diagnose, and very mortal if not treated. Our study investigated the effects of astaxanthin, which is known to have potent antioxidant properties and is also known to have anti-inflammatory effects on ischemia-reperfusion (I/R) injury. METHODS: A total of 32 healthy Wistar albino female rats were used in our study. Subjects were randomized and equally divided into 4 groups; control (laparotomy group only), I/R (transient mesenteric ischemia group only), astaxanthin 1 mg/kg and 10 mg/kg doses. The transient ischemia time was 60 minutes and the reperfusion time was 120 minutes. Tissue samples were taken from intracardiac blood and terminal ileum after reperfusion. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) from blood samples, interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNFα), Caspase-3, P53 tests from terminal ileum were studied. Tissue samples were also taken for histopathological evaluation. RESULTS: At the end of the study, both doses of astaxanthin were found to significantly reduce MDA level, CAT, and SOD enzymatic activity, whereas higher doses of astaxanthin significantly reduced MDA level, CAT, and SOD enzyme activities. In addition, cytokines such as TNFα, IL-1 and IL-6 were found to be reduced at both doses of astaxanthin, but only significantly inhibited at higher doses. We observed that inhibition of apoptosis reduced caspase-3 activity and P53 and deoxyribonucleic acid (DNA) fragmentation. CONCLUSION: Astaxanthin, a potent antioxidant, and anti-inflammatory, significantly reduces ischemia and reperfusion injury, especially when used at a dose of 10 mg/kg. These data need to be confirmed by larger animal series and clinical studies.

Vitamin K levels in Fibromyalgia Syndrome Patients and Their Associations with Pain, Disease Activity, Quality of Life and Inflammatory Cytokines.

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic pain condition that requires multidisciplinary treatment. Vitamin K is an antioxidant that plays a role in many reactions in the body, and its effectiveness in FMS has not been studied before. AIM: We aimed to evaluate vitamin K levels in FMS patients and their relationship with pain, disease activity, quality of life, and inflammatory cytokines. METHOD: Eighty-eight female patients with FMS and 87 controls were included in the study. Vitamin K and inflammatory cytokine (interleukin-6 [IL-6], IL-8, tumor necrosis factor [TNF]-alfa) serum levels were measured in both groups. Visual Analog Scale (VAS), Fibromyalgia Impact Questionnaire (FIQ), and Short Form-36 (SF-36) scales were used. RESULTS: No statistically significant differences in vitamin K levels between the two groups, and no relationships were found between these levels and pain, FIQ, SF-36, and inflammatory cytokines (p > .05). While IL-6 and TNF-alpha levels were found to be high in the FMS group compared with the control group (p < .05), no difference in IL-8 levels was noted (p > .05). In the FMS group, positive correlations were found between IL-6 and FIQ, and between TNF-alpha and physical role difficulty(p > .05). CONCLUSIONS: Overall, the results of this study do not provide any evidence of an association between FMS and vitamin K levels. However, high IL-6 and TNF-alpha levels suggest that low-intensity inflammation may accompany FMS and have a negative impact on physical activity. Future studies are needed to determine the relationship between vitamin K and FMS.

Genetic Polymorphism on Chromosome 4q25 (rs17570669) May Predict Recurrence After Successful Electrical Cardioversion in Patients with Persistent Atrial Fibrillation.

OBJECTIVE: Direct current electrical cardioversion (DCCV) is an effective rhythm-control option for patients with atrial fibrillation (AF). Despite initial success, a high recurrence rate remains a significant challenge. There is limited data on the genetic predictors of AF recurrence following successful DCCV. In this study, we aimed to evaluate whether 11 single nucleotide polymorphisms (SNPs) previously associated with AF are also linked to recurrence after DCCV in the Turkish population. METHODS: Seventy-five patients with persistent AF, who achieved stable sinus rhythm following DCCV, were included in the study. The patients were prospectively monitored for the onset of AF recurrence. Clinical characteristics and SNPs were analyzed and compared between patients who experienced recurrence and those who did not. RESULTS: The average age of the patients was 61.9 ± 11.5, and 33 (44%) were female. Over an average follow-up period of 17.0 (11.0-25.0) months, AF recurrence was observed in 38 patients (50.7%). A SNP in the PITX2 gene (rs17570669) (OR: 9.00, 95% Confidence Interval (CI): 1.28-63.02) and another in the ZFHX3 gene (rs2106261) (OR: 8.96, 95% CI: 1.03-77.66) were notably associated with AF recurrence in the additive model (P = 0.027 and 0.047, respectively). Multivariate Cox regression analysis revealed that the rs17570669 SNP was the sole independent predictor of AF recurrence (Hazard Ratio (HR): 3.59, 95% CI: 1.05-12.21, P = 0.040). CONCLUSION: The SNP in the paired-like homeodomain 2 (PITX2) gene (rs17570669) emerges as an independent predictor for AF recurrence after successful electrical cardioversion.

A Novel Finding of an HLA Allele's and a Haplotype's Relationship with SARS-CoV-2 Vaccine-Associated Subacute Thyroiditis.

Subacute thyroiditis (SAT) is a thyroid disease associated with viral infections. Its relationship with major histocompatibility complex (MHC) antigens was shown before. SAT cases triggered by different types of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been reported. In this study, human leukocyte antigen (HLA) genotypes of 27 SAT patients (13 vaccine-associated (V-SAT) and 14 non-SARS-CoV-2-infection non-vaccine-associated (non-V-SAT)) were compared with those of 362 healthy donors. HLA analyses were performed with low-resolution DNA-based sequence-specific oligonucleotide or sequence-specific primer methods. Statistical analyses were performed using IBM SPSS Statistics 25 and Stata/MP 14.1 with the hapipf function. Allele and haplotype frequencies were estimated by PyPop and gene[RATE] tool programs. The allele frequencies of HLA-A*11, HLA-B*35, and HLA-C*04 were higher in the patient groups. Both the allele frequency of HLA-A*11 and the haplotype frequency of A*11-B*35-C*04 were higher in the V-SAT group. The A*11-B*35-C*04 haplotype, including all three loci of MHC class I genes, is shown to be associated with the disease for the first time, especially in the V-SAT group. This finding will contribute to a better understanding of the etiopathogenesis of vaccine-associated SAT and the role of HLA genotypes in the functioning mechanisms of the SARS-CoV-2 vaccines.

Effects of the probiotic, Lactobacillus rhamnosus GG, on ulcer pathogenesis, HSP70 stress protein and nitric oxide levels in stress induced ulcer.

Peptic ulcer is a gastric or duodenal mucosal injury; psychological stress may participate in development of the lesions. Heat shock protein-70 (HSP70) is a molecular chaperone that is responsible for cellular healing; it is an early biomarker of cellular damage. Nitric oxide (NO) is an intra- and intercellular messenger in the gastrointestinal system that protects mucosal integrity. Lactobacillus rhamnosus is among the microflora of the intestinal tract; it is resistant to gastric acidity. We investigated the efficacy of L. rhamnosus administration on ulcer pathogenesis, stress protein HSP70 and NO levels in experimental stress induced ulcer. The proton pump inhibitor, pantoprazole, was used for comparison with the gastroprotective effect of the probiotic. We administered 10 mg/kg pantoprazole and L. rhamnosus at doses of 3 × 108 cfu/ml (M1), 15 × 108 cfu/ml (M5), 30 × 108 cfu/ml (M10) to rats according to McFarland-1, McFarland-5, McFarland-10 standards, respectively. Rats were stressed by immobilization at 4 °C, then sacrificed. The pH, amounts of gastric mucus, NO and HSP70 levels were measured and the histological structure of stomach was assessed. We found increased NO levels in the M5 group and increased HSP70 expression in the pantoprazole group. Significant epithelial damage was observed in the stressed groups and minimal epithelial damage was observed in M5 group compared to controls. The probiotic, L. rhamnosus, may be useful for preventing stress induced ulcers.

Capsaicin Alters the Expression of Genetic and Epigenetic Molecules In Hepatocellular Carcinoma Cell.

Capsaicin is a natural product which is extracted from pepper and has the potential to be used in cancer treatment because of its anti- proliferative effects. The aim of the study was to determine the effect of capsaicin on the hepatocellular carcinoma cell proliferation and the expressions of related genetic markers as Ki-67, PI3K/AKT/mTOR and epigenetic markers as miR-126 and piR-Hep-1. The inhibitory concentration of capsaicin in HepG2 cells was determined. piR-Hep-1 and miR-126 expressions and Ki-67, PI3K, AKT and mTOR gene expressions were examined by RT-PCR. The inhibitory concentration of capsaicin for HepG2 cells was 200 nM and the decreased proliferation was observed at 24th hour. As epigenetic markers, an up regulation of miR-126 and down regulation of piR-Hep-1 expression were determined after treatment. Moreover, Ki-67, PI3K and mTOR gene expressions decreased while AKT gene expression increased after the treatment (p<0.001). According to the obtained data, capsaicin has an impact on proliferation both genetically and epigenetically. Furthermore, treatment of capsaicin effects miR-126 and piR-Hep-1 expressions which effect carcinogenesis in different way. Moreover, there are some clues which indicate that these two small non-coding RNA might affect each other and share the same target molecules post-transcriptionally.

The effect of Tai Chi on functional mobility, balance and falls in Parkinson's disease: A systematic review and meta-analysis of systematic reviews.

BACKGROUND: The aim of the study was to evaluate the effect of Tai Chi on functional mobility, balance and falls in Parkinson's disease. MATERIALS AND METHODS: A comprehensive literature search was conducted to identify the systematic reviews and meta-analyses up to the end of October 2021. 601 studies were identified, and 16 of them were included in our study. RESULTS: According to our meta-analysis; there was a significant effect of Tai Chi on balance (SMD, -0.777 95% CI -0.921 to -0.633; p = 0.000), functional mobility (SMD, -0.719 95% CI -0.944 to -0.494; p = 0.000), and falls (SMD, -0.456 95% CI -0.668 to -0.245; p = 0.000) in PD. CONCLUSION: Our systematic review and meta-analysis found significant effects of Tai Chi on functional mobility, balance and falls in patients with PD.

The relationship of retinopathy of prematurity with brain-derivated neurotrophic factor, vascular endotelial growth factor-A, endothelial PAD domain protein 1 and nitric oxide synthase 3 gene polymorphisms.

BACKGROUND: In addition to risk factors such as low birth weight and uncontrolled oxygen therapy, genetic predisposition is also thought to play a role in the development of retinopathy of prematurity (ROP). In our study, we aimed to analyze single-nucleotide polymorphisms (SNPs) in VEGFA, EPAS1, BDNF and NOS3 genes in infants who develop ROP. MATERIALS AND METHODS: Seventy-five mild-moderate and 73 severe ROP cases were included in this study. Eleven different SNPs regions that located in VEGFA, EPAS1, BDNF and NOS3 genes were analysed by SnapShot technique and compared between two groups by the multiple logistic regression analysis. RESULTS: Statistically significant results were obtained in 8 of the 11 SNPs. It was observed that the excess of mutant alleles in four (VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744) of these regions increased ROP severity and treatment requirement (p < .001, p < .001, p = .022, p = .004, respectively) while the excess of mutant alleles in the other four regions (VEGFA rs833061, BDNF rs7929344, EPAS1 rs1867785 and rs1868085) showed that ROP severtiy was milder and eliminated the need for treatment (p < .001, p = .019, p = .017, p = .017, respectively). CONCLUSIONS: Considering the results of our study, it was seen that besides the known environmental and demographic factors in ROP pathogenesis, genetic predisposition also had an effect on the clinic and course of ROP. Polymorphisms of VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744 were found to be associated with severe ROP. More studies involving different populations cases are needed to confirm these findings and enlighten the etiology of ROP.

Prognostic significance of tumor budding in muscle invasive urothelial carcinomas of the urinary bladder.

OBJECTIVE: The aim of the present study was to analyze the prognostic significance of tumor budding in muscle-invasive urothelial carcinomas of the urinary bladder, and also to determine an optimal threshold value in evaluation. PATIENTS AND METHODS: The study included 108 patients diagnosed with muscleinvasive conventional urothelial carcinoma between 2010 and 2020. Tumor budding was evaluated on H&E-stained slides. The critical tumor budding number was determined with the "receiver operating characteristics (ROC)" curve. Cases with a tumor budding number of ≤6 were categorized as low, and cases with >6 as high tumor budding. RESULTS: The univariate Cox proportional hazards regression model for recurrence-free survival showed that lymphovascular invasion (P = 0.001), tumor budding (P = 0.012), pT stage (T4 vs. T2) (P = 0.005), and lymph node metastasis (P = 0.009) were significantly associated with recurrence-free survival. The multivariate Cox proportional hazards regression model utilizing backward stepwise (wald) method revealed that only LVI (P = 0.001) was independent risk factor for recurrence-free survival. The univariate Cox analysis showed that lymphovascular invasion (P = 0.001), tumor budding (P = 0.004), pT stage (T4 vs. T2) (P = 0.003), and lymph node metastasis (P = 0.001) were significantly associated with overall survival. The multivariate Cox analysis (backward stepwise (wald) method) revealed that tumor focality (P = 0.018), pT stage (T4 vs. T2) (P = 0.015), and lymphovascular invasion (P = 0.002) were independent factors for overall survival. CONCLUSIONS: Our findings suggested that the evaluation of tumor budding may be a useful parameter for predicting outcome in patients with muscle-invasive bladder cancer.

Potential associations between variants of genes encoding regulators of inflammation, and mediators of inflammation in type 2 diabetes and insulin resistance.

WHAT IS KNOWN AND OBJECTIVE: Type 2 diabetes (T2DM) is a multigenic disease that develops with impaired ß-cell function and insulin sensitivity and has a high prevalence worldwide. A cause often postulated for type 2 diabetes is chronic inflammation. It has been suggested that inflammatory regulators can inhibit insulin signal transduction and that inflammation is involved in insulin resistance (IR) and the pathogenesis of type 2 diabetes. In this direction, we aimed to investigate the gene variants of MyD88 (rs1319438, rs199396), IRAK4 (rs1461567, rs4251513, rs4251559) and TRAF6 (rs331455, rs331457) and serum levels of COX-2, NF-κB, iNOS in T2DM and IR. METHODS: The MyD88, IRAK4 and TRAF6 variations were genotyped in 100 newly diagnosed T2DM patients and 100 non-diabetic individuals using The MassARRAY® Iplex GOLD SNP genotyping method. The COX-2, iNOS and NF-κB levels were measured in serum samples with the sandwich-ELISA method. Results were analysed using SPSS Statistics software and the online FINNETI program. RESULTS AND DISCUSSION: In our study, a total of the 7 variants in the MyD88, IRAK4 and TRAF6 genes were genotyped, and as a result, no relationship was found between most of these variants and the risk of type 2 diabetes and insulin resistance (p > 0.05). Only, the rs1461567 variant of the IRAK4 gene was significant in the heterozygous model (CC vs. CT), and the CT genotype was most frequent in diabetic individuals compared with the non-diabetics (p = 0.033). Additionally, COX-2 and iNOS levels were found to be associated with diabetes and insulin resistance (p < 0.05). WHAT IS NEW AND CONCLUSION: Our results show that high COX-2 and iNOS levels are associated with T2DM, besides MyD88, IRAK4 and TRAF6 gene variations may not be closely related to type 2 diabetes and insulin resistance. Nevertheless, studies in this pathway with a different population and a large number of patients are important.

Role of Notch, IL-1 and leptin expression in colorectal cancer.

An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors. It has been shown that the inhibition of leptin-induced angiogenesis resulted in decreased levels of vascular endothelial growth factor (VEGF)/VEGFR2, hypoxia inducible factor (HIF) 1α, NF-κB, IL-1 and Notch and reduced the tumor growth in breast cancer. Leptin induces angiogenesis in breast cancer either by upregulating VEGFR2 in endothelial cells or by increasing VEGF/VEGFR2 expression through the Notch, IL-1 and leptin crosstalk outcome (NILCO) pathway. NILCO is a novel mechanism that interacts with proinflammatory and proangiogenic signals, which are critical for cell proliferation and angiogenesis in cancer. Several studies have shown that components of NILCO may affect human cancer incidence and progression. However, to the best of our knowledge, the interactions between Notch, IL-1 and leptin in human colorectal cancer have not been yet studied at the molecular level. The aim of the present study was to investigate the expression levels of genes related to the NILCO pathway in human colorectal cancer specimens. The current results demonstrated that leptin, leptin receptor (ObR) b, Notch-1, Notch-4, IL-1α, IL-1ß, IL-1R, IL-6, JAK-2, STAT-1, STAT-3, VEGFA, VEGFR1, VEGFR2, TNF-α and NF-κB mRNA expression levels in the cancer tissue were increased compared with the normal tissue. No significant changes in the mRNA expression levels of Jagged-1, HIF-1α and TNF receptor 1 were observed. Western blotting revealed that the protein expression levels of IκB were increased in the cancer tissue compared with normal tissue, whereas HIF-1α and phosphorylated STAT-1 levels were decreased. IL-6 and VEGFA plasma concentrations were statistically raised and the leptin plasma concentration was also raised, although significantly, patients with cancer compared with control individuals. Together, the present findings indicated that Notch, IL-1 and leptin may serve a crucial role in the development of colorectal cancer.

Genetic variants associated with atrial fibrillationand long-term recurrence after catheter ablation for atrialfibrillation in Turkish patients.

OBJECTIVE: Genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF) and can predict AF recurrence after catheter ablation in different populations. However, there exists no such data for the Turkish population. We aimed to investigate whether 11 SNPs in the PITX2, ZFHX3, EPHX2, CAV1, TBX5, TGF-1, and SCN10A were related to AF and whether these SNPs can predict long-term atrial tachyarrhythmia (ATa) recurrence after pulmonary vein isolation (PVI) for AF in Turkish patients. METHODS: A total of 245 consecutive patients with non-valvular AF (44.9% men, mean age: 60.2±13.2 years, 65.3% paroxysmal AF) and 50 age- and sex-matched controls were included in this analysis. The clinical features and genetic variants were compared between the 2 groups. Of the 245 patients, 128 who underwent PVI with second-generation cryoballoon were further examined for long-term recurrence after the procedure. RESULTS: Four SNPs in PITX2 were significantly associated with AF (rs10033464_T: OR 3.29, 95%CI: 1.38-7.82, p=0.007; rs6838973_T: OR 3.06, 95% CI 1.36-6.87, p=0.007; rs3853445_C: OR 2.84, 95%CI: 1.27-6.36, p=0.011; rs17570669_T: OR 4.03, 95% CI: 1.71-9.51, p=0.001). Among these patients who underwent PVI, one locus in CAV1 (rs3807989_G: OR 4.50, 95% CI 1.04-19.31, p=0.043) and early recurrence (OR: 8.06, 95% CI: 2.12-30.55, p=0.002) predicted long-term AF recurrence after catheter ablation. CONCLUSION: Significant associations exists between 4 SNPs in PITX2 and AF (rs10033464, rs6838973, rs3853445, and rs17570669) in Turkish patients. In addition, 1 genetic variant in CAV1 (rs3807989) and early recurrence can predict long-term ATa recurrence after catheter ablation.