Perceived functional disabilities among rheumatoid arthritis patients

The aim of this study was to determine from patient perspective the most relevant physical functions when estimating the functional disabilities, and to estimate the perceived relative influence of them. Structured telephone interviews were conducted among 143 RA patients. The subjects were asked to name functions and activities in their everyday life, which were affected by RA. After this, they were asked to score each of the named item with a scale from 0 to 100. These were combined with earlier collected data on sociodemographic background and clinical status. Listed activities were grouped to functional disabilities and further categorized according to joints, limbs and body areas. One or more functional disabilities affecting everyday life because of RA was mentioned by 87.4%, altogether 354 mentions. The most commonly mentioned disabilities were walking and opening jars. However, the most commonly mentioned disabilities were not those with highest perceived disabilities. Of the 59 different types of disabilities mentioned, 25 were connected with movements of the shoulder, 30 with elbow, 40 with wrist, and 37 with fingers. Movements of the back were involved in 20 mentioned disabilities, hip and knee both in 8, and ankles in 6. Disabilities related to lower extremity functions were considered most disabling. In conclusion, to describe RA patients’ functional disability, the measured functions should be those which the patients themselves consider relevant and causing disability. Furthermore, the studied functional measures ought to be weighted according to the relative influence of each function to the patients.     

The obesity-cancer link: lessons learned from a fatless mouse

Current dogma suggests that the positive correlation between obesity and cancer is driven by white adipose tissue that accompanies obesity, possibly through excess secretion of adipokines. Recent studies in fatless A-Zip/F1 mice, which have undetectable adipokine levels but display accelerated tumor formation, suggest that adipokines are not required for the enhanced tumor development. The A-Zip/F-1 mice are also diabetic and display elevated circulating levels of other factors frequently associated with obesity (insulin, insulin-like growth factor-1, and proinflammatory cytokines) and activation of several signaling pathways associated with carcinogenesis. In view of this information, the risk factors underlying the obesity-cancer link need to be revisited. We postulate that the pathways associated with insulin resistance and inflammation, rather than adipocyte-derived factors, may represent key prevention and therapeutic targets for disrupting the obesity-cancer link.     

Accelerated tumor formation in a fatless mouse with type 2 diabetes and inflammation

Epidemiologic studies show a positive association between obesity and cancer risk. In addition to increased body adiposity and secretion of fat-derived hormones, obesity is also linked to insulin resistance, type 2 diabetes, and chronic inflammation. We used the fatless A-ZIP/F-1 transgenic mouse to dissociate the relative role of each of these underlying factors in the development of cancer. These mice are unique in that they do not have white fat but do develop type 2 diabetes. In two cancer models, the classic two-stage skin carcinogenesis protocol and the C3(1)/T-Ag transgenic mouse mammary tumor model, A-ZIP/F-1 mice displayed higher tumor incidence, tumor multiplicity, and decreased tumor latency than wild-type mice. We examined circulating levels of adipokines, growth factors, and cytokines. As expected, adipokines (i.e., leptin, adiponectin, and resistin) were undetectable or found at very low levels in the blood of fatless mice. However, insulin, insulin-like growth factor-I, growth hormone, vascular endothelial growth factor, and proinflammatory Th2 cytokines, such as interleukin (IL)-1beta, IL-4, and IL-6, were elevated in A-ZIP/F-1 mice. Additionally, we examined multiple phosphorylated proteins (i.e., protein kinase B/Akt and ErbB2/HER-2 kinase) associated with cancer development. Results show that many of these phosphorylated proteins were activated specifically in the A-ZIP/F-1 skin but not in the wild-type skin. These findings suggest that adipokines are not required for the promotion of tumor development and thus contradict the epidemiologic data linking obesity to carcinogenesis. We postulate that insulin resistance and inflammation are responsible for the positive correlation with cancer observed in A-ZIP/F-1 mice.     

C3 binding glycoprotein from Cuscuta europea induced different cytokine profiles from human PBMC compared to other plant and bacterial immunomodulators

The immunomodulatory properties of bioactive agents include the ability to induce cytokine production by the activated target cell. The effect of immunomodulatory C3 binding glycoprotein isolated from Cuscuta europea on the induction of human PBMC cytokine synthesis and the cell viability was investigated. Isolated PBMC from healthy donors were cultured for 24 h with C3bgp. We also studied the influence of C3bgp on the cytokine production in LPS, PHA, PWM and Dex treated PBMC. The quantitative determination of TNF-alpha, IL-12, IL-6 and IL-10 was performed in culture supernatant by ELISA. Results obtained demonstrated that C3bgp induced proinflammatory and immunoregulatory cytokine production, in the highest degree IL-12, followed by IL-6 and in lower degree TNF-alpha. IL-12 quantity was significantly increased in C3bgp stimulated cultures in comparison with LPS, PHA and PWM stimulated PBMC. C3bgp also increased IL-12 in PHA or PWM stimulated cultures, but not in LPS stimulated culture. C3bgp significantly increased IL-6 production compared to the PHA and PWM but not to LPS stimulation. On the other side, C3bgp inhibited IL-10 production after LPS, PHA and PWM stimulation. Cell viability in C3bgp stimulated cultures retained on the same level from 72 to 120 h of culturing, in contrast to LPS and PHA stimulated cultures. Based on the results presented, we conclude that the C3bgp exhibited immunomodulatory properties on the human PBMC. The ability of PDTC and Dex to down-regulate the effect of C3bgp on the proinflammatory cytokine production suggests that a part of the mechanism of action of C3bgp is mediated through NF-kB signal transduction pathway.     

Functional genetic polymorphisms in interleukin-12B gene in association with systemic lupus erythematosus

Genetic polymorphisms in cytokine genes, which influence gene expression, may have an important impact on SLE susceptibility and severity. The aim of this study was to examine the possible influence of two functional polymorphisms in cis-regulatory regions of IL12B gene in the susceptibility and clinical symptoms of SLE in Bulgarian patients. Female SLE patients (n = 141) and 124 healthy women were included in the study. Genotyping for the IL12B A/C polymorphism in 3′UTR was performed by restriction fragment length polymorphisms PCR assay and for the IL12Bpro polymorphism by allele-specific PCR. Genotype-22 of IL12Bpro polymorphism was overrepresented among women with SLE (28 vs. 17%; OR = 1.875; 95% CI: 1.037 ÷ 3.390; P = 0.037). Respectively, a higher frequency of allele-2 was found in patients than in controls (51% vs. 40%; OR = 1.566; 95% CI: 1.110 ÷ 2.210; P = 0.011). Also, we found significantly elevated frequency of genotype-22 of IL12Bpro polymorphism among SLE patients who were simultaneously carrier of genotype-AA of SNP in 3′UTR. Women with both homozygous genotypes, genotype-AA of SNP in 3′UTR and genotype-22 of IL12Bpro polymorphism, had a 2.1-fold significantly elevated risk for SLE development. The carrying of genotype-11 of IL12Bpro polymorphism was positively associated with hematological and neuropsychiatric manifestations of SLE. We have provided evidence that the IL12Bpro polymorphism was associated with SLE development among Bulgarian women. Although a strong individual effect of SNP in 3′UTR of IL12B was not detected, we found that genotype-22 of IL12Bpro was predominantly combined with genotype-AA of SNP in 3′UTR among SLE patients and this combination elevates the risk of SLE.     

Correlates of HIV infection and being unaware of HIV status among soon-to-be-released Ukrainian prisoners

Introduction

Prisoners bear a disproportionate burden of Ukraine''s volatile and transitional HIV epidemic, yet little is known in Eastern Europe about HIV testing, treatment and HIV-related risk among prisoners.

Methods

A nationally representative biobehavioural health survey linked with serological testing was conducted among soon-to-be released prisoners in 13 Ukrainian prisons from June to November 2011.

Results

Among 402 participants, 78 (19.4%) tested HIV seropositive of whom 38 (50.7%) were previously unaware of their HIV status. Independent correlates of HIV infection included drug injection (AOR=4.26; 95% CI: 2.23–8.15), female gender (AOR=2.00; 95% CI: 1.06–3.78), previous incarceration (AOR=1.99; 95% CI: 1.07–3.70) and being from Southern Ukraine (AOR=5.46; 95% CI: 2.21–13.46). Those aware of being HIV-positive reported significantly more pre-incarceration sex- and drug-related HIV risk behaviours than those who were unaware.

Conclusions

Routine rather than risk-based HIV testing and expansion of opioid substitution and antiretroviral therapy among prisoners is urgently needed to reduce HIV transmission in volatile transitional HIV epidemics.     

Obesity Accelerates Mouse Mammary Tumor Growth in the Absence of Ovarian Hormones

Obesity increases incidence and mortality of breast cancer in postmenopausal women. Mechanisms underlying this association are poorly understood. Suitable animal models are needed to elucidate potential mechanisms for this association. To determine the effects of obesity on mammary tumor growth, nonovariectomized and ovariectomized C57BL/6 mice of various body weights (lean, overweight, and obese) were implanted subcutaneously with mammary tumor cells from syngeneic Wnt-1 transgenic mice. In mice, the lean phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. Ovariectomy delayed Wnt-1 tumor growth consistent with the known hormone responsiveness of these tumors. However, obesity accelerated tumor growth in ovariectomized but not in nonovariectomized animals. Diet-induced obesity in a syngeneic mouse model of breast cancer enhanced tumor growth, specifically in the absence of ovarian hormones. These results support epidemiological evidence that obesity is associated with increased breast cancer incidence and mortality in postmenopausal but not premenopausal women. In contrast, maintaining a lean body weight phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status.     

Willingness to pay for improvement of physical function among rheumatoid arthritis patients as measured by Health Assessment Questionnaire

The main objective of this study was to assess the symptoms and functional difficulties caused by rheumatoid arthritis through application of the willingness to pay (WTP) method. Structured questionnaire study was conducted among 242 RA patients. The subjects were asked to evaluate their functional capacity using visual analog scales (VAS) for all the 20 questions in the Health Assessment Questionnaire (HAQ). Each VAS was followed by a question asking how much the respondent would be willing to pay on a monthly basis for a 50% improvement with the function in question. These were combined with later collected data on clinical status and use of RA-related health services. The average WTP varied greatly in the examined 20 different functions. The total WTP average on a 50% improved functional capacity amounted to € 567.05 per month. Patients with lower functional capacity (HAQ 1.2 or more) were ready to contribute significantly (p < 0.001) more (705 euros/month) than those with better functional status (199 euros/month). Subjects, whose financial standing was better, reported a higher total WTP (r = 0.218, p < 0.01). On average, the total WTP of the respondents equaled 18.44% of the disposable net monthly income per person of the household. However, the variation was quite substantial. WTP among patients with rheumatoid arthritis was best depicted through the functional capacity of the patient, the possible time the patient had retired, and the global feeling of pain. In conclusion, monetary value is a concrete way of portraying subjective valuation. WTP method is suitable for assessing functional deficits of rheumatoid arthritis.