No Change in Perceptual or Chronotropic Outcome When Altering Preferred Step Frequency for a Short Duration

IIntroduction: Millions of individuals incorporate jogging into their physical activity routines as a leisurely pursuit and as a way to achieve positive health outcomes. People appear to choose jogging speed and the associated step frequency on pure, natural preference. Understandably, kinesthetics are important, but another important underlying factor is metabolic cost. The purpose of this work was to investigate if preferred step frequency (at a preferred jogging pace) also minimizes perceived effort (Borg Rating of Perceived Exertion, 6-20; RPE) and chronotropic stress (heart rate; HR) during a ten-minute activity bout when compared with step frequencies altered by 5%. Methods: Recreationally-trained male subjects underwent two testing visits. The first visit was used to establish RPE and HR responses during a 10-minute jogging activity at preferred speed and step frequency. On a subsequent visit, between two and four days later, with preferred speed maintained, subjects were guided by metronome to strike at either 95% or 105% of their preferred step frequency. The 10-minute runs were randomized, crossed-over, and separated by 20 minutes. RPE and HR were analyzed by repeated measures ANOVA. Results: Fourteen subjects (age: 21.1 ± 0.95; body mass index: 23.2 ± 2.5) enrolled. Preferred jogging speed (speed. 6.4 ± 1.0 miles per hour; 10.2 ± 1.6 kilometers per hour) and step frequency (steps. 161.2 ± 10.3 steps/minute) were determined at the first visit, along with RPE (11.3 ± 1.7) and HR (166.4 ± 12.7). At the second visit, preferred speed was maintained while the frequency of foot-strike was altered. Neither differences in RPE (p = 0.252; 11.3 ± 1.7, 11.6 ± 1.9, 11.8 ± 1.5) nor HR (p = 0.547; 166.4 ± 12.7, 164.7 ± 14.9, 165.2 ± 15.3) were different when comparing the preferred, 95%, and 105% step frequency trials, respectively. Although anecdotal, some subjects verbalized displeasure with the change in pace and most all appeared to markedly alter the initial foot strike phase of the gait to meet the directed foot strike tempo. Discussion: Our data must be interpreted cautiously. While altering step frequency by 5% for a short duration does not appear to alter an individual’s RPE or HR appreciably, the result during longer duration activity may not be the same. In addition, the implications for biomechanical loading and metabolic cost were not presently investigated

A powerful intervention: general practitioners' use of sickness certification in depression

<b>Background</b> Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.<p></p> <b>Methods</b> A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.<p></p> <b>Results</b> A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.<p></p> <b>Conclusions</b> GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

Sex differences in brain tumor glutamine metabolism reveal sex-specific vulnerabilities to treatment

BACKGROUND: Brain cancer incidence and mortality rates are greater in males. Understanding the molecular mechanisms that underlie those sex differences could improve treatment strategies. Although sex differences in normal metabolism are well described, it is currently unknown whether they persist in cancerous tissue. METHODS: Using positron emission tomography (PET) imaging and mass spectrometry, we assessed sex differences in glioma metabolism in samples from affected individuals. We assessed the role of glutamine metabolism in male and female murine transformed astrocytes using isotope labeling, metabolic rescue experiments, and pharmacological and genetic perturbations to modulate pathway activity. FINDINGS: We found that male glioblastoma surgical specimens are enriched for amino acid metabolites, including glutamine. Fluoroglutamine PET imaging analyses showed that gliomas in affected male individuals exhibit significantly higher glutamine uptake. These sex differences were well modeled in murine transformed astrocytes, in which male cells imported and metabolized more glutamine and were more sensitive to glutaminase 1 (GLS1) inhibition. The sensitivity to GLS1 inhibition in males was driven by their dependence on glutamine-derived glutamate for α-ketoglutarate synthesis and tricarboxylic acid (TCA) cycle replenishment. Females were resistant to GLS1 inhibition through greater pyruvate carboxylase (PC)-mediated TCA cycle replenishment, and knockdown of PC sensitized females to GLS1 inhibition. CONCLUSION: Our results show that clinically important sex differences exist in targetable elements of metabolism. Recognition of sex-biased metabolism may improve treatments through further laboratory and clinical research. FUNDING: This work was supported by NIH grants, Joshua\u27s Great Things, the Siteman Investment Program, and the Barnard Research Fund

LAB/NTAL Facilitates Fungal/PAMP-induced IL-12 and IFN-γ Production by Repressing β-Catenin Activation in Dendritic Cells.

Fungal pathogens elicit cytokine responses downstream of immunoreceptor tyrosine-based activation motif (ITAM)-coupled or hemiITAM-containing receptors and TLRs. The Linker for Activation of B cells/Non-T cell Activating Linker (LAB/NTAL) encoded by Lat2, is a known regulator of ITAM-coupled receptors and TLR-associated cytokine responses. Here we demonstrate that LAB is involved in anti-fungal immunity. We show that Lat2−/− mice are more susceptible to C. albicans infection than wild type (WT) mice. Dendritic cells (DCs) express LAB and we show that it is basally phosphorylated by the growth factor M-CSF or following engagement of Dectin-2, but not Dectin-1. Our data revealed a unique mechanism whereby LAB controls basal and fungal/pathogen-associated molecular patterns (PAMP)-induced nuclear β-catenin levels. This in turn is important for controlling fungal/PAMP-induced cytokine production in DCs. C. albicans- and LPS-induced IL-12 and IL-23 production was blunted inLat2−/− DCs. Accordingly, Lat2−/− DCs directed reduced Th1 polarization in vitro and Lat2−/−mice displayed reduced Natural Killer (NK) and T cell-mediated IFN-γ production in vivo/ex vivo. Thus our data define a novel link between LAB and β-catenin nuclear accumulation in DCs that facilitates IFN-γ responses during anti-fungal immunity. In addition, these findings are likely to be relevant to other infectious diseases that require IL-12 family cytokines and an IFN-γ response for pathogen clearance

A randomized single blind crossover trial comparing leather and commercial wrist splints for treating chronic wrist pain in adults

<p>Abstract</p> <p>Background</p> <p>To compare the effectiveness of a custom-made leather wrist splint (LS) with a commercially available fabric splint (FS) in adults with chronic wrist pain.</p> <p>Methods</p> <p>Participants (N = 25, mean age = 54) were randomly assigned to treatment order in a 2-phase crossover trial. Splints were worn for 2 weeks, separated by a one-week washout period. Outcomes were assessed at baseline and after each splint phase using the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Canadian Occupational Performance Measure (COPM) and Jamar dynamometer by an observer blinded to treatment allocation.</p> <p>Results</p> <p>Both styles of wrist splint significantly reduced pain (effect size LS 0.79, FS 0.43), improved hand function and increased grip strength compared to baseline (all p < 0.05) with no increase in wrist stiffness. There was a consistent trend for the LS to be superior to the FS but this was statistically significant only for patient perceived occupational performance (p = 0.008) and satisfaction (p = 0.015). Lastly, 72% of patients preferred the custom-made leather splint compared to the commercially available splint.</p> <p>Conclusion</p> <p>Leather wrist splints were superior to a commercially available fabric splint for the short-term relief of pain and dysfunction.</p

Dethroning historical reputations: Universities, museums and the commemoration of benefactors

The campaigns in universities across the world to reject, rename and remove historic benefactions have brought the present into collision with the past. In Britain the attempt to remove a statue of one of Oxford’s most famous benefactors, the imperialist Cecil Rhodes, has spread to other universities and their benefactors, and now also affects civic monuments and statues in towns and cities across the country. In the United States, memorials to leaders of the Confederacy in the American Civil War and to other slaveholders have been the subject of intense dispute. Should we continue to honour benefactors and historic figures whose actions are now deemed ethically unacceptable? How can we reconcile the views held by our ancestors with those we now hold today? Should we even try, acknowledging, in the words of the novelist L. P. Hartley, that ‘the past is another country; they do things differently there’? The essays in this interdisciplinary collection are drawn from a conference at the Institute of Historical Research in the University of London. Historians, fundraisers, a sociologist and a museum director examine these current issues from different perspectives, with an introductory essay by Sir David Cannadine, president of the British Academy. Together they explore an emerging conflict between the past and present, history and ideology, and benefactors and their critics

New Developments in Understanding Cardiovascular Disease and the Implications for Social Work

Cardiovascular disease is now viewed as an inflammatory disease. An index of chronic inflammation (viz., C-Reactive Protein) is as good a predictor of heart attacks as are fats in blood. The data suggest that stressful events are so closely associated with chronic inflammatory states, that the body’s stress response can be viewed as an inflammatory state. This paper summarizes and explains the link between stress and cardiovascular disease. Negative health outcomes, particularly for cardiovascular diseases, are higher among those of lower socio-economic status. Differential stress among socio-economic tiers is considered as an explanation for the disparities. The literature linking cardiovascular risk factors to the stressors of workplace unfairness and lack of control over working conditions is reviewed. The role of the stressor of racism in explaining the higher rates of cardiovascular mortality in African Americans is discussed. Finally, for societies with wider gaps in income between the rich and the poor, increased stress is explored as a possible explanation for the diminished health outcomes found across all socio-economic tiers. The implications for social work direct practice and macro-practice are considered

Randomized Controlled Caregiver Mediated Joint Engagement Intervention for Toddlers with Autism

This study aimed to determine if a joint attention intervention would result in greater joint engagement between caregivers and toddlers with autism. The intervention consisted of 24 caregiver-mediated sessions with follow-up 1 year later. Compared to caregivers and toddlers randomized to the waitlist control group the immediate treatment (IT) group made significant improvements in targeted areas of joint engagement. The IT group demonstrated significant improvements with medium to large effect sizes in their responsiveness to joint attention and their diversity of functional play acts after the intervention with maintenance of these skills 1 year post-intervention. These are among the first randomized controlled data to suggest that short-term parent-mediated interventions can have important effects on core impairments in toddlers with autism. Clinical Trials #: NCT00065910