Stat5 as a diagnostic marker for leukemia

The Jak-Stat-Socs pathway is an important component of cytokine receptor signaling. Not surprisingly, perturbation of this pathway is implicated in diseases of hematopoietic and immune origin, including leukemia, lymphoma and immune deficiencies. This review examines the role of a key component of this pathway, Stat5. This has been shown to be activated in a variety of leukemias and myeloproliferative disorders, including downstream of a range of key oncogenes where it has been shown to play an important role in mediating their effects. Therefore, Stat5 represents a useful pan-leukemia/myeloproliferative disorder diagnostic marker and key therapeutic end point, as well as representing an attractive therapeutic target for these disorders.

Is television viewing time a marker of a broader pattern of sedentary behavior?

Background: Television (TV) viewing time is associated with abnormal glucose metabolism, the metabolic syndrome, and risk of type 2 diabetes; associations are stronger and more consistent in women. One explanation of this difference may be that TV viewing is a marker of an overall pattern of sedentary behavior in women.

Purpose: We sought to examine associations of TV viewing time with other sedentary behaviors and with leisure-time physical activity in a large sample of Australian adults.

Methods: Adults aged between 20 and 65 years (n=2,046) completed a  self-administered questionnaire on TV viewing, five other leisure-time sedentary behaviors, and leisure-time physical activity. Mean adjusted time spent in other sedentary behaviors and in physical activity was compared across TV-time  categories previously shown to be associated with abnormal glucose  metabolism.

Results: After adjustment for body mass index and sociodemographic variables, women’s time spent watching TV was associated positively with time in other sedentary behaviors and negatively with leisure-time physical activity, but no such associations were observed in men.

Conclusions: TV viewing time may be a robust marker of a sedentary lifestyle in women but not in men. Gender differences in the pattern of sedentary behaviors may explain at least in part the gender differences in the previously reported associations of TV viewing time with biological attributes related to type 2   diabetes.

Skin temperature as a noninvasive marker of haemodynamic and perfusion status in adult cardiac surgical patients : an observational study

Objective
Foot temperature has long been advocated as a reliable noninvasive measure of cardiac output despite equivocal evidence. The aim of this pilot study was to investigate the relationship between noninvasively measured skin temperature and the more invasive core-peripheral temperature gradients (CPTGs), against cardiac output, systemic vascular resistance, serum lactate, and base deficit.

Research methodology
The study was of a prospective, observational and correlational design. Seventy-six measurements were recorded on 10 adults postcardiac surgery. Haemodynamic assessments were made via bolus thermodilution. Skin temperature was measured objectively via adhesive probes, and subjectively using a three-point scale.

Setting
The study was conducted within a tertiary level intensive care unit.

Results
Cardiac output was a significant predictor for objectively measured skin temperature and CPTG (p = .001 and p = .004, respectively). Subjective assessment of skin temperature was significantly related to cardiac output, systemic vascular resistance, and serum lactate (p < .001, respectively).

Conclusions
These results support the utilisation of skin temperature as a noninvasive marker of cardiac output and perfusion. The use of CPTG was shown to be unnecessary, given the parallels in results with the less invasive skin temperature parameters. A larger study is however required to validate these findings.

Epithelial cell folate is an accurate marker when compared with whole tissue biopsy folate for examining the role of folate status in colorectal cancer

Background – Epidemiological studies have shown low folate status is associated with colorectal cancer. Colonic tissue folate levels at different stages of cancer development should give important information, but different methodologies to extract the colonic tissue folates have been used. This has hampered progress in defining the relationship between systemic and tissue folate levels.
Objective – To evaluate two methods of colonic tissue preparation for estimation of total folate content.
Design – Whole tissue punch biopsy samples were obtained from the descending colon of 31individuals following a normal colonoscopy. Blood samples were obtained for the determination of plasma homocysteine (Hcy), red cell folate (RCF), methylenetetrahydrofolate reductase 677C>T genotype, and serum vitamin B12 and folate. Colonic tissue folate was measured both in washed whole tissue biopsies and in epithelial cells isolated from tissue biopsies.
Outcomes - Whole biopsy and epithelial cell folate concentrations were significantly correlated (R=.375; P=.038). Hcy was inversely correlated with both measures (R=-.365; P=.043 and R=-.364; P=.044 respectively). RCF was significantly correlated with isolated epithelial cell folate (R=.477; P=.007) but not with whole tissue biopsy folate (R=.264; P=.151). There were no significant associations between serum and colonic folate in this study.
Conclusion - Both methods are useful for comparing systemic and localised tissue folate status but epithelial cells may provide more reliable data.

Interaction of the Akt substrate, AS160, with the glucose transporter 4 vesicle marker protein, insulin-regulated aminopeptidase

Insulin-regulated aminopeptidase (IRAP), a marker of glucose transporter 4 (GLUT4) storage vesicles (GSVs), is the only protein known to traffic with GLUT4. In the basal state, GSVs are sequestered from the constitutively recycling endosomal system to an insulin-responsive, intracellular pool. Insulin induces a rapid translocation of GSVs to the cell surface from this pool, resulting in the incorporation of IRAP and GLUT4 into the plasma membrane. We sought to identify proteins that interact with IRAP to further understand this GSV trafficking process. This study describes our identification of a novel interaction between the amino terminus of IRAP and the Akt substrate, AS160 (Akt substrate of 160 kDa). The validity of this interaction was confirmed by coimmunoprecipitation of both overexpressed and endogenous proteins. Moreover, confocal microscopy demonstrated colocalization of these proteins. In addition, we demonstrate that the IRAP-binding domain of AS160 falls within its second phosphotyrosine-binding domain and the interaction is not regulated by AS160 phosphorylation. We hypothesize that AS160 is localized to GLUT4-containing vesicles via its interaction with IRAP where it inhibits the activity of Rab substrates in its vicinity, effectively tethering the vesicles intracellularly.

β-blockers reduce bone resorption marker in early postmenopausal women

Background: There is evidence to suggest that β-blockers used in the management of cardiovascular disease may also modulate bone metabolism and reduce bone fragility.

Aim: The study aimed to determine the association between β-blocker use, serum markers of bone turnover and bone loss in early postmenopausal women.

Subjects and methods: In this observational study, we evaluated β-blocker exposure in association with serum levels of C-telopeptide and bone-specific alkaline phosphatase, and rates of bone loss. β-blocker use, concomitant therapy and lifestyle were documented for 197 women (50–59 years), 175 of whom had changes in whole body bone mineral density monitored over a 2–year period.

Results: Twenty-four β-blocker users were identified at baseline. After controlling for concomitant use of hormone therapy, C-telopeptide levels were 6.7% lower among β-blocker users (p = 0.02). No association was detected between bone-specific alkaline phosphatase and β-blocker use. Analysis of 15 β-blocker users and 152 non-users identified 2 years post-baseline showed that levels of C-telopeptide but not bone-specific alkaline phosphatase were predictors of adjusted rates of bone loss (p = 0.008 and p>0.05, respectively). Adjusted rates of bone loss were −0.001 ± 0.026 g cm−2 over 2 years for the users and −0.004 ± 0.025 g cm−2 over 2 years for non-users, but this difference was not significant.

Conclusion: β-blockers might suppress bone resorption with relative preservation of bone formation. A study with greater power is required to determine whether β-blocker use is associated with lower rates of bone loss.

Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Background: There is evidence that myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by activation of immune, inflammatory, oxidative and nitrosative stress (IO&NS) pathways. The present study was carried out in order to examine whether ME/CFS is accompanied by increased levels of plasma peroxides and serum oxidized LDL (oxLDL) antibodies, two biomarkers of oxidative stress.

Material/Methods: Blood was collected from 56 patients with ME/CFS and 37 normal volunteers. Severity of ME/CFS was measured using the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.

Results: Plasma peroxide concentrations were significantly higher in patients with ME/CFS than in normal controls. There was a trend towards significantly higher serum oxLDL antibodies in ME/CFS than in controls. Both biomarkers contributed significantly in discriminating between patients with ME/CFS and normal controls. Plasma peroxide and serum oxLDL antibody levels were both significantly related to one of the FF symptoms.

Conclusions: The results show that ME/CFS is characterized by increased oxidative stress.

Dossier Chris Marker : the suffering image

Dossier Chris Marker: The Suffering Image is a study of a late-modern chiasmus, impersonal-personal agency, as it comes to expression in the works of French artist and filmmaker, Chris Marker, as the dynamic interplay of political and subjective agency. As chiasmus, the complementary halves of this often-apocalyptic dynamis (a semi-catastrophic, temporal or historical force-field) also – arguably – secretly agree to meet, through the work of art, in the futural. Consistent with the classical figure of concordia discors, these irreducible warring aspects of life experience are, in fact, resolved in an atemporal and ahistorical moment that inhabits the work of art from its inception. This redemptive aspect in art is also the ultimate gesture of the artwork as “mask” or “screen” for forces that reside beyond the frame of the image or work, as its proverbial Other, or within the frame, as other to that Other. A topological “knot,” or ontological “problem,” it is this very conflict that animates all of Marker’s extensive works – filmic and otherwise.

Osteopaenia - a marker of low bone mass and fracture risk

Areal bone mineral density is commonly categorised into normal bone mineral density, osteopaenia and osteoporosis on the basis of nominal thresholds recommended by the World Health Organization. However, bone mineral density is a continuous variable and there is a strong association between lower bone mineral density and greater risk for fracture. Fracture risk is not negligible in persons with moderate deficits in bone mineral density. Although absolute fracture risk is greatest for individuals with osteoporosis, more than half of the fractures arise from those with osteopaenia, and even normal bone mineral density, a probable consequence of greater numbers of individuals at risk in these categories. However, areal bone mineral density measurements used commonly in clinical practice do not detect differences in bone tissue properties, geometry and microarchitecture, which contribute to bone strength. Newer technologies such as high-resolution peripheral computed tomography have the advantage of assessing trabecular and cortical components of bone separately, in addition to geometric characteristics of the skeleton. Quantifying these parameters and considering clinical risk factors that affect fracture risk independent of bone quantity and quality, may better discriminate between high- and low-risk individuals. This would improve the decision-making for targeting appropriate interventions, either lifestyle or medication, to reduce thepublic health burden of fractures.