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.
Objectives: To investigate the role of serum apolipoprotein (apo) B levels in predicting metabolic syndrome (MS), hypertension, atherogenic dyslipidemia and type II diabetes. Methods: Prospective ...evaluation of 1125 men and 1223 women, aged 28-74 years, participating in the survey 1997/1998 who had serum apo B determinations and were followed-up for a mean 5.9 years. Tertiles of apo B were formed by cut points by 120 and 95 mg/dl. MS was defined by modified ATPIII criteria. Results: Apo B values exhibited no significant difference among sexes. Low-density lipoprotein (LDL)-cholesterol and triglycerides were their leading determinants on linear regression analysis. By logistic regression analyses, the top versus bottom apo B tertile predicted significantly newly developing MS in both sexes separately with two-fold relative risks (RRs) (P<0.02) and the development of high triglyceride/low high-density lipoprotein-cholesterol dyslipidemia with nearly threefold RRs (P=0.001), after adjustment for waist circumference, C-reactive protein (CRP), physical activity grade and family income category. Development of hypertension was predicted only in women by the apo B top tertile (fully adjusted RR 1.71 95% CI 1.001; 2.92), while the significance of the prediction regarding age-adjusted diabetes in women (RR 1.86 95% CI 1.04; 3.36) attenuated after adjustment for the stated confounding factors. Conclusions: Apo B concentrations, which reflect the number of small, dense LDL particles in plasma, are a significant predictor of cardiometabolic risk among adults with a high prevalence of MS, independent of waist circumference and CRP.
5-Fluorouracil (5-FU) is an anti-metabolite that is in clinical use for treatment of several cancers. In cells, it is converted into three distinct fluoro-based nucleotide analogs, which interfere ...with DNA synthesis and repair, leading to genome impairment and, eventually, apoptotic cell death. Current knowledge states that in certain cell types, 5-FU-induced stress is signaling through a p53-dependent induction of tumor necrosis factor-receptor oligomerization required for death-inducing signaling complex formation and caspase-8 activation. Here we establish a role of calcium (Ca(2+)) as a messenger for p53 activation in response to 5-FU. Using a combination of pharmacological and genetic approaches, we show that treatment of colon carcinoma cells stimulates entry of extracellular Ca(2+) through long lasting-type plasma membrane channels, which further directs posttranslational phosphorylation of at least three p53 serine residues (S15, S33 and S37) by means of calmodulin (CaM) activity. Obstructing this pathway by the Ca(2+)-chelator BAPTA (1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid) or by inhibitors of CaM efficiently reduces 5-FU-induced caspase activities and subsequent cell death. Moreover, ectopic expression of p53 S15A in HCT116 p53(-/-) cells confirmed the importance of a Ca(2+)-CaM-p53 axis in 5-FU-induced extrinsic apoptosis. The fact that a widely used therapeutic drug, such as 5-FU, is operating via this pathway could provide new therapeutic intervention points, or specify new combinatorial treatment regimes.
In addition to marshalling immune and inflammatory responses, transcription factors of the NF-κB family control cell survival. This control is crucial to a wide range of biological processes, ...including B and T lymphopoiesis, adaptive immunity, oncogenesis and cancer chemoresistance. During an inflammatory response, NF-κB activation antagonizes apoptosis induced by tumor necrosis factor (TNF)-α, a protective activity that involves suppression of the Jun N-terminal kinase (JNK) cascade. This suppression can involve upregulation of the Gadd45-family member Gadd45β/Myd118, which associates with the JNK kinase MKK7/JNKK2 and blocks its catalytic activity. Upregulation of XIAP, A20 and blockers of reactive oxygen species (ROS) appear to be important additional means by which NF-κB blunts JNK signaling. These recent findings might open up entirely new avenues for therapeutic intervention in chronic inflammatory diseases and certain cancers; indeed, the Gadd45β-MKK7 interaction might be a key target for such intervention.
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.
Objective: This study aimed to examine the attitudes and concerns of chemotherapy patients related to COVID-19 vaccination and determine factors associated with their vaccine behavior. Patients and ...Methods: A cross-sectional, descriptive study was conducted with 300 patients who received chemotherapy in the oncology outpatient clinic of a University Hospital in Istanbul in October 2021. Based on our power calculation, a minimum sample size of 264 patients was needed. However, we recruited a sample of 300 to increase the power of the study. Data were collected online using a patient information form and the Attitudes Towards the COVID-19 Vaccine Scale. The data were analyzed using descriptive statistics and parametric tests. Results: The participants had a mean age of 55.64±13.80 years, 56.7% were women, 64% were married, 38.3% were high school graduates, and 35.7% were homemakers. Age, education level, and chronic disease were associated only with negative attitudes towards the COVID-19 vaccine; gender was associated with positive attitudes. Being vaccinated against COVID-19 was associated with 99% lower negative attitudes and 66.9 times higher positive attitudes towards the COVID-19 vaccine, while men had 76% lower positive attitudes than women. Conclusions: Overall, patients receiving chemotherapy had a favorable attitude toward and high acceptance of the COVID-19 vaccine.
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