Stage Call: Cardiovascular Reactivity to Audition Stress in Musicians

Auditioning is at the very center of educational and professional life in music and is associated with significant psychophysical demands. Knowledge of how these demands affect cardiovascular responses to psychosocial pressure is essential for developing strategies to both manage stress and understand optimal performance states. To this end, we recorded the electrocardiograms (ECGs) of 16 musicians (11 violinists and 5 flutists) before and during performances in both low- and high-stress conditions: with no audience and in front of an audition panel, respectively. The analysis consisted of the detection of R-peaks in the ECGs to extract heart rate variability (HRV) from the notoriously noisy real-world ECGs. Our data analysis approach spanned both standard (temporal and spectral) and advanced (structural complexity) techniques. The complexity science approaches—namely, multiscale sample entropy and multiscale fuzzy entropy—indicated a statistically significant decrease in structural complexity in HRV from the low- to the high-stress condition and an increase in structural complexity from the pre-performance to performance period, thus confirming the complexity loss theory and a loss in degrees of freedom due to stress. Results from the spectral analyses also suggest that the stress responses in the female participants were more parasympathetically driven than those of the male participants. In conclusion, our findings suggest that interventions to manage stress are best targeted at the sensitive pre-performance period, before an audition begins

Developing a placebo-controlled trial in surgery:issues of design, acceptability and feasibility

BACKGROUND: Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. METHODS: Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). RESULTS: There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. CONCLUSIONS: Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. TRIAL REGISTRATION NUMBER: The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007

Functional Characterization of EngAMS, a P-Loop GTPase of Mycobacterium smegmatis

Bacterial P-loop GTPases belong to a family of proteins that selectively hydrolyze a small molecule guanosine tri-phosphate (GTP) to guanosine di-phosphate (GDP) and inorganic phosphate, and regulate several essential cellular activities such as cell division, chromosomal segregation and ribosomal assembly. A comparative genome sequence analysis of different mycobacterial species indicates the presence of multiple P-loop GTPases that exhibit highly conserved motifs. However, an exact function of most of these GTPases in mycobacteria remains elusive. In the present study we characterized the function of a P-loop GTPase in mycobacteria by employing an EngA homologue from Mycobacterium smegmatis, encoded by an open reading frame, designated as MSMEG_3738. Amino acid sequence alignment and phylogenetic analysis suggest that MSMEG_3738 (termed as EngAMS) is highly conserved in mycobacteria. Homology modeling of EngAMS reveals a cloverleaf structure comprising of α/β fold typical to EngA family of GTPases. Recombinant EngAMS purified from E. coli exhibits a GTP hydrolysis activity which is inhibited by the presence of GDP. Interestingly, the EngAMS protein is co-eluted with 16S and 23S ribosomal RNA during purification and exhibits association with 30S, 50S and 70S ribosomal subunits. Further studies demonstrate that GTP is essential for interaction of EngAMS with 50S subunit of ribosome and specifically C-terminal domains of EngAMS are required to facilitate this interaction. Moreover, EngAMS devoid of N-terminal region interacts well with 50S even in the absence of GTP, indicating a regulatory role of the N-terminal domain in EngAMS-50S interaction

Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In the past several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in glioblastoma treatment. However, no study has demonstrated the status of global <it>HDAC </it>expression in gliomas and its possible correlation to the use of HDACis. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas.</p> <p>Methods</p> <p>Forty-three microdissected patient tumor samples were evaluated. The histopathologic diagnoses were 20 low-grade gliomas (13 grade I and 7 grade II) and 23 high-grade gliomas (5 grade III and 18 glioblastomas). Eleven normal cerebral tissue samples were also analyzed (54 total samples analyzed). mRNA expression of class I, II, and IV <it>HDACs </it>was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene <it>β-glucuronidase</it>. Protein levels were evaluated by western blotting.</p> <p>Results</p> <p>We found that mRNA levels of class II and IV <it>HDACs </it>were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, <it>p </it>< 0.05). The protein levels of class II HDAC9 were also lower in high-grade astrocytomas than in low-grade astrocytomas and normal brain tissue. Additionally, we found that histone H3 (but not histone H4) was more acetylated in glioblastomas than normal brain tissue.</p> <p>Conclusion</p> <p>Our study establishes a negative correlation between <it>HDAC </it>gene expression and the glioma grade suggesting that class II and IV <it>HDACs </it>might play an important role in glioma malignancy. Evaluation of histone acetylation levels showed that histone H3 is more acetylated in glioblastomas than normal brain tissue confirming the downregulation of <it>HDAC </it>mRNA in glioblastomas.</p

Promoting Functional Health in Midlife and Old Age: Long-Term Protective Effects of Control Beliefs, Social Support, and Physical Exercise

Previous studies have examined physical risk factors in relation to functional health, but less work has focused on the protective role of psychological and social factors. We examined the individual and joint protective contribution of control beliefs, social support and physical exercise to changes in functional health, beyond the influence of health status and physical risk factors in middle-aged and older adults. Given that functional health typically declines throughout adulthood, it is important to identify modifiable factors that can be implemented to maintain functioning, improve quality of life, and reduce disability.We conducted a national longitudinal study, Midlife in the United States (MIDUS), with assessments in 1995-1996 and 2004-2006, and 3,626 community-residing adults, aged 32 to 84, were included in the analyses. Functional health (Physical Functioning subscale of the SF-36) and protective factors were measured at both occasions. While controlling for socio-demographic, health status, and physical risk factors (large waist circumference, smoking, and alcohol or drug problems), a composite of the three protective variables (control beliefs, social support, and physical exercise) at Time 1 was significantly related to functional health change. The more of these factors at Time 1, the better the health maintenance over 10 years. Among middle-aged and older adults, declines in health were significantly reduced with an increased number of protective factors.Age-related declines in health were reduced among those with more protective factors up to a decade earlier in life. Modifiable psychological, social, and physical protective factors, individually and in the aggregate, are associated with maintenance of functional health, beyond the damaging effects of physical risk factors. The results are encouraging for the prospect of developing interventions to promote functional health and for reducing public health expenditures for physical disability in later life

The Wnt-dependent signaling pathways as target in oncology drug discovery

Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer’s disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways