Myonuclear alterations associated with exercise are independent of age in humans.

Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with the nuclear lamina protein lamin A regulating nuclear shape, nuclear mechanics and ultimately gene expression. Defective lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than those from untrained individuals. Complementary to this, exercise resulted in increased levels of lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan. KEY POINTS: The nucleus plays an active role in translating forces into biochemical signals. Myonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function. Here, striking differences are presented in myonuclear shape and mechanics associated with exercise, in both young and old humans. Myonuclei from trained individuals were more spherical, less deformable and contained a thicker nuclear lamina than untrained individuals. It is concluded that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan.

Common mental disorders among Irish jockeys: prevalence and risk factors.

OBJECTIVE: Jockeys compete in a sport, horseracing, renowned for its physical and psychological demands. Previous research has identified that common mental disorders (CMDs) may be prevalent among this unique population of athletes. The aim of the present study was to further explore the prevalence of CMDs among jockeys and to test for associations with potential risk factors. METHODS: An anonymous survey was distributed to professional jockey online. Self-report screening tools for four CMDs (psychological distress, depression, generalized anxiety, and adverse alcohol use) were included alongside predictor variables from questionnaires assessing for burnout, career satisfaction, social support, and the contemplation of retirement. Binary logistic regression was used to explore associations between CMDs (present versus not present) and risk factors. Eighty-four professional jockeys completed the questionnaire (response rate = 52%). RESULTS: In total, 79% of jockeys met the threshold for at least one CMD. Prevalence (%) of CMD varied as follows: adverse alcohol (61%), depression (35%), generalized anxiety (27%), and psychological distress (19%). Burnout, career (dis)satisfaction, lower levels of social support, and the contemplation of retirement increased the odds of meeting the criteria for CMDs. CONCLUSION: The findings indicate that jockeys report CMD symptoms at comparable rates to athletes in other sports. The study was the first to highlight potential risk factors as predictors of CMDs among jockeys, including burnout, career satisfaction, and the current contemplation of retirement. Screening tools for the risk factors demonstrated may, therefore, provide useful in the early identification of CMDs among jockeys. The development of jockey-specific assessment tools, education programmes, and interventions may help better understand and support the mental health of jockeys.

Health Analytics as a Service with Artemis Cloud: Service Availability.

Critical care units internationally contain medical devices that generate Big Data in the form of high speed physiological data streams. Great opportunities exist for systemic and reliable approaches for the analysis of high speed physiological data for clinical decision support. This paper presents the instantiation of a Big Data analytics based Health Analytics as-a-Service model. The availability results of the deployment of two instances of Artemis Cloud to support two neonatal ICUs (NICUs) in Ontario Canada are presented.

Monolithically multi-color lasing from an InGaN microdisk on a Si substrate.

An optically pumped multi-color laser has been achieved using an InGaN/GaN based micro-disk with an undercut structure on a silicon substrate. The micro-disk laser has been fabricated by means of a combination of a cost-effective microsphere lithography technique and subsequent dry/wet etching processes. The microdisk laser is approximately 1 µm in diameter. The structure was designed in such a way that the vertical components of the whispering gallery (WG) modes formed can be effectively suppressed. Consequently, three clean lasing peaks at 442 nm, 493 nm and 522 nm have been achieved at room temperature by simply using a continuous-wave diode laser as an optical pumping source. Time-resolved micro photoluminescence (PL) measurements have been performed in order to further confirm the lasing by investigating the excitonic recombination dynamics of these lasing peaks. A three dimensional finite-difference-time-domain (FDTD) simulation has been used for the structure design.

Risk assessment tools in criminal justice and forensic psychiatry: The need for better data.

Violence risk assessment tools are increasingly used within criminal justice and forensic psychiatry, however there is little relevant, reliable and unbiased data regarding their predictive accuracy. We argue that such data are needed to (i) prevent excessive reliance on risk assessment scores, (ii) allow matching of different risk assessment tools to different contexts of application, (iii) protect against problematic forms of discrimination and stigmatisation, and (iv) ensure that contentious demographic variables are not prematurely removed from risk assessment tools.

Naegleria fowleri: Diagnosis, Pathophysiology of Brain Inflammation, and Antimicrobial Treatments.

Primary amoebic meningoencephalitis (PAM) is a very rare disease with a high mortality rate. PAM is caused by Naegleria fowleri, an amoeba which resides in freshwater lakes and ponds and can survive in inadequately chlorinated pools ( Lopez, C.; Budge, P.; Chen, J., et al. Primary amebic meningoencephalitis: a case report and literature review . Pediatr. Emerg. Care 2012 , 28 , 272 - 276 ). In the past 50 years, there have been over 130 cases of Naegleria induced PAM in the United States with only three known survivors; one survivor was diagnosed and treated at Arkansas Children's Hospital. Successful treatment of PAM started with a rapid diagnosis, extensive antimicrobial therapy including an investigational medication miltefosine, supportive care, an intraventricular shunt, and hypothermia. These treatments address different aspects of the disease process. Increased understanding of the diagnosis and treatment of PAM is important especially for patients who present with meningitis-like findings during the summer months.

Numerical model for intraosseous infusion of the human calvarium for hydrocephalus shunting.

Hydrocephaly is the defective absorption of cerebrospinal fluid (CSF) into the blood stream. This work is an experimental and computational fluid dynamic modelling study to determine the permeability of the diploë as a potential receptor for CSF. Human calvariae were studied by micro-CT to measure their porosity, the area of flow and develop model geometry. Pressure-flow measurements were conducted on specimens to determine their permeability in the physiological and transverse flow directions to compare with numerical results. The overall porosity and permeability of the calvaria were spatially variable. Results suggest an order of magnitude increase in permeability for a 14% increase in overall porosity based on a small number of samples. Numerical results fell within the experimental infusion tests results. Due to the difficulty and ethical considerations in obtaining adolescent skull samples to perform large-scale testing, the developed model will be invaluable.

Remote, real-time monitoring and analysis of vital signs of neonatal graduate infants.

This paper presents a system for the remote monitoring of a newborn infant's physiological data outside the Neonatal Intensive Care Unit. By providing a simple means for parents to enable monitoring, and physicians a simple mobile application to monitor live and historical physiological information, this system provides the insight once only possible in an Intensive Care Unit. The system utilizes a variety of connectivity means such as Wi-Fi and 3G to facilitate the communication between a multitude of industry standard vital sign monitor and a remote server. A system trial monitoring an infant to simulate neonatal graduate monitoring has determined the system was able to successfully transmit 99.99% of data generated from the vital sign monitor.

Elemental imaging of MRI contrast agents: benchmarking of LA-ICP-MS to MRI.

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been used to map the spatial distribution of magnetic resonance imaging (MRI) contrast agents (Gd-based) in histological sections in order to explore synergies with in vivo MRI. Images from respective techniques are presented for two separate studies namely (1) convection enhanced delivery of a Gd nanocomplex (developmental therapeutic) into rat brain and (2) convection enhanced delivery, with co-infusion of Magnevist (commercial Gd contrast agent) and Carboplatin (chemotherapy drug), into pig brain. The LA technique was shown to be a powerful compliment to MRI not only in offering improved sensitivity, spatial resolution and signal quantitation but also in giving added value regarding the fate of administered agents (Gd and Pt agents). Furthermore simultaneous measurement of Fe enabled assignment of an anomalous contrast enhancement region in rat brain to haemorrhage at the infusion site.

A stuck hemodialysis central venous catheter.

BACKGROUND: A growing number of hemodialysis patients are dependent upon central venous catheters (CVCs) for long-term vascular access. Although many complications of CVCs have been documented, the phenomenon of the stuck catheter is described relatively infrequently. CASE REPORT: We describe a case where attempts to remove the line by exploration of the jugular insertion site in theater were unsuccessful and the line was internalized. DISCUSSION: The case is then discussed with all available cases in the literature to suggest principles of managing and preventing the stuck catheter phenomenon.

Isolated intraspinal germinoma in a child with congenital adrenal hyperplasia.

STUDY DESIGN: Case report. OBJECTIVE: To report an intramedullary germinoma associated with congenital adrenal hyperplasia (CAH). METHOD: We report a 14-year-old white male with CAH who was found to have an intramedullary germinoma of the conus medullaris. Presentation and evaluation were for progressive urinary incontinence. A brief review of relevant literature was presented. RESULTS: Cases where germinomas have occurred simultaneously with CAH have been identified intracranially, but to our knowledge, this is the first case of CAH and intramedullary spinal cord germinoma occurring simultaneously. CONCLUSION: Although rare, primary intramedullary germinomas do occur. The association between CAH and spinal cord germinoma should be considered by clinicians.

Impact of statins and angiotensin-converting enzyme inhibitors on mortality of subjects hospitalised with pneumonia.

Recent studies suggest that statins and angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for some types of infections. The present study aimed to examine the association of outpatient use of these medications on 30-day mortality for subjects aged >65 yrs and hospitalised with community-acquired pneumonia. A retrospective national cohort study was conducted using the Department of Veterans Affairs administrative data including subjects aged >/=65 yrs hospitalised with community-acquired pneumonia, and having >/=1 yr of prior Veterans Affairs outpatient care. In total, 8,652 subjects were identified with a mean age of 75 yrs, 98.6% were male, and 9.9% of subjects died within 30 days of presentation. In this cohort, 18.1% of subjects were using statins and 33.9% were using ACE inhibitors. After adjusting for potential confounders, current statin use (odds ratio (OR) 0.54, 95% confidence interval (CI) 0.42-0.70) and ACE inhibitor use (OR 0.80, 95% CI 0.68-0.89) were significantly associated with decreased 30-day mortality. Use of statins and angiotensin-converting enzyme inhibitors prior to admission is associated with decreased mortality in subjects hospitalised with community-acquired pneumonia. Randomised controlled trials are needed to examine whether the use of these medications in patients hospitalised with community-acquired pneumonia may be beneficial.

Testicular microlithiasis as a familial risk factor for testicular germ cell tumour.

Testicular microlithiasis (TM) is characterised by small intratesticular calcifications, which can be visualised by ultrasound. Men with testicular germ cell tumour (TGCT) have a higher frequency of TM than men without TGCT. To clarify the association between TGCT and TM and to investigate the relationship between TGCT susceptibility and TM, we recruited TGCT patients with and without family history of TGCT, unaffected male relatives and healthy male controls from the UK. Testicular ultrasound data were analysed from 328 men. Testicular microlithiasis was more frequent in TGCT cases than controls (36.7 vs 17.8%, age adjusted P<0.0001) and in unaffected male relatives than controls (34.5 vs 17.8%, age adjusted P=0.02). Testicular germ cell tumour case and matched relative pairs showed greater concordance for TM than would be expected by chance (P=0.05). We show that TM is present at a higher frequency in relatives of TGCT cases than expected by chance indicating that TM is a familial risk factor for TGCT. Although the familiality of TM could be due to shared exposures, it is likely that there exists a genetic susceptibility to TM that also predisposes to TGCT. We suggest that TM is an alternative manifestation of a TGCT susceptibility allele.

Determination of pattern centre in EBSD using the moving-screen technique.

The 'moving-screen' or 'pattern magnification' method of calibration for electron backscatter diffraction (EBSD) was reformulated to develop a high-precision technique requiring no crystallographic knowledge of the specimen and no initial estimates of the calibration parameters. The technique depends upon the accurate displacement of the screen and camera assembly. Corresponding points are selected, interactively, from EBSD patterns. It is suggested that, as an alternative, the selection of points from the Hough transform could lead to a completely automated routine.

COPD is associated with increased mortality in patients with community-acquired pneumonia.

Patients with chronic obstructive pulmonary disease (COPD) who develop community-acquired pneumonia (CAP) may experience worse clinical outcomes. However, COPD is not included as a distinct diagnosis in validated instruments that predict mortality in patients with CAP. The aim of the present study was to evaluate the impact of COPD as a comorbid condition on 30- and 90-day mortality in CAP patients. A retrospective observational study was conducted at two hospitals. Eligible patients had a discharge diagnosis and radiological confirmation of CAP. Among 744 patients with CAP, 215 had a comorbid diagnosis of COPD and 529 did not have COPD. The COPD group had a higher mean pneumonia severity index score (105+/-32 versus 87+/-34) and were admitted to the intensive care unit more frequently (25 versus 18%). After adjusting for severity of disease and processes of care, CAP patients with COPD showed significantly higher 30- and 90-day mortality than non-COPD patients. Chronic obstructive pulmonary disease patients hospitalised with community-acquired pneumonia exhibited higher 30- and 90-day mortality than patients without chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease should be evaluated for inclusion in community-acquired pneumonia prediction instruments.

Evidence-based guidelines meet the real world: the case of diabetes care.

OBJECTIVE: Improving diabetes care in the U.S. is critical because diabetes rates are increasing dramatically, particularly among minority and low-income populations. Although evidence-based practice guidelines for diabetes have been widely disseminated, many physicians fail to implement them. The objective of this study was to explore what happens to diabetes practice guidelines in real-world clinical settings. RESEARCH DESIGN AND METHODS: A qualitative research design was used. Open-ended semistructured interviews lasting 1-2 h were conducted with 32 key informants (physicians, certified diabetes educators, researchers, and agency personnel) selected for their knowledge of diabetes care in South Texas, an area with a high diabetes prevalence and a large proportion of minority and low-income patients. RESULTS: Health professionals stress that contextual factors are more important barriers to optimal diabetes care than physician knowledge and attitudes. Barriers exist at multiple levels and are interrelated in a complex manner. Examples include the following: time constraints and practice economics in the private practice setting; the need to maintain referral relationships and maldistribution of professionals in the practice community; low awareness and low socioeconomic status among patients; and lack of access for low-income patients, low reimbursement, and insufficient focus on prevention in the U.S. health care system. CONCLUSIONS: Contextual barriers must be addressed in order for diabetes practice guidelines to be implemented in real-world clinical practice. Suggested changes include an increased focus on prevention, improvements in health care delivery for chronic diseases, and increased attention to the special needs of minority and low-income populations.

Duck hepatitis B photoinactivation bydimethylmethylene blue in RBC suspensions.

BACKGROUND: Dimethylmethylene blue (DMMB) has been used to photoinactivate a number of model viruses, including VSV, in RBC suspensions under conditions that preserve in vitro RBC properties during storage. The relative sensitivity of duck HBV (DHBV) and VSV to photoinactivation by DMMB was investigated by performing an indirect immunofluorescence assay (IFA) using primary duck hepatocyte (PDH) cultures or a standard plaque assay for the respective viruses. STUDY DESIGN AND METHODS: DMMB was added to 45-percent Hct, WBC-reduced, oxygenated AS-3 RBCs at 10-, 1-, and 0.1-microM concentrations. Samples (1-mm thick) were illuminated with 5.4-mW per cm(2) of red light for 2 or 9 seconds. Unilluminated samples without DMMB or with 10 microM DMMB served as control. RESULTS: DHBV and VSV were rapidly photoinactivated by DMMB in a concentration and light-dose-dependent fashion. Neither virus was substantially inactivated by incubation with DMMB in the dark. For a given light exposure, DHBV required a concentration of DMMB one-one hundredth that of VSV to achieve approximately the same level of inactivation. CONCLUSION: DHBV appears to be considerably more sensitive than VSV to DMMB photoinactivation. Photoinactivation in 45-percent Hct RBCs can be achieved in seconds by using micromolar quantities of dye.

Role of singlet diradicals in reactions of 2-carbenabicyclo[3.2.1]octa-3,6-diene.

The generation of 2-carbenabicyclo[3.2.1]octa-3,6-diene (1) results in the formation of C(8)H(8) hydrocarbons endo-6-ethynylbicyclo[3.1.0]hex-2-ene (4), semibullvalene (5), and 5-ethynyl-1,3-cyclohexadiene (6), and C(8)H(10) hydrocarbons bicyclo[3.2.1]octa-2,6-diene (7), tricyclo[3.2.1.0(4,6)]oct-2-ene (8), and tetracyclo[3.3.0.0(2,8)0(4,6)]octane (9). Focus is placed on three mechanistic pathways for the formation of the C(8)H(10) hydrocarbon fraction: (a) abstraction of hydrogen by triplet carbene 1T to produce an equilibrating set of monoradicals, (b) interconversion of triplet carbene 1T into tricyclic triplet diradical 19T and tetracyclic triplet diradical 20T, and (c) interconversion of singlet 1S with analogous singlet diradical 19S and 20S. Ab initio calculations at the (U)B3LYP/6-311+G(3df,2p)//(U)B3LYP/6-31G(d,p) and broken spin symmetry UBS B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d,p) levels rule out choices (a) and (b) and are consistent with the singlet diradical process.

A comparison of diabetic foot ulcer patients managed in VHA and non-VHA settings.

OBJECTIVE: To compare patients with diabetes and new onset foot ulcers treated in Veterans Health Administration (VHA) and non-VHA settings. METHODS: The treatment of patients with new onset diabetic foot ulcers was prospectively monitored in three VHA and three non-VHA hospitals and outpatient settings until ulcer healing, amputation, or death. RESULTS: Of the 302 individuals enrolled in this study, 47% were veterans receiving VHA care. There were no significant differences between veterans and nonveterans in baseline wound classification, diabetes severity, or comorbid conditions. Veterans received significantly fewer sharp debridements, total contact casts, and custom inserts than their nonveteran counterparts, and they had significantly more x-rays, local saline irrigations, IV antibiotics, and prescriptions for bed rest. The percentage of amputations was higher in veterans but did not achieve statistical significance. CONCLUSIONS: Many commonly held stereotypes of veteran men were not found. Veterans and nonveterans with foot ulcers were similar in terms of health and foot history, diabetes severity, and comorbid conditions. There was considerable variation in treatment of diabetic foot ulcers between VHA and non-VHA care. Yet this variation did not result in statistically significant differences in ulcer outcomes.