The Inexorable Spread of a Newly Arisen Neo-Y Chromosome

A newly arisen Y-chromosome can become established in one part of a species range by genetic drift or through the effects of selection on sexually antagonistic alleles. However, it is difficult to explain why it should then spread throughout the species range after this initial episode. As it spreads into new populations, it will actually enter females. It would then be expected to perform poorly since it will have been shaped by the selective regime of the male-only environment from which it came. We address this problem using computer models of hybrid zone dynamics where a neo-XY chromosomal race meets the ancestral karyotype. Our models consider that the neo-Y was established by the fusion of an autosome with the ancestral X-chromosome (thereby creating the Y and the ‘fused X’). Our principal finding is that sexually antagonistic effects of the Y induce indirect selection in favour of the fused X-chromosomes, causing their spread. The Y-chromosome can then spread, protected behind the advancing shield of the fused X distribution. This mode of spread provides a robust explanation of how newly arisen Y-chromosomes can spread. A Y-chromosome would be expected to accumulate mutations that would cause it to be selected against when it is a rare newly arrived migrant. The Y can spread, nevertheless, because of the indirect selection induced by gene flow (which can only be observed in models comprising multiple populations). These results suggest a fundamental re-evaluation of sex-chromosome hybrid zones. The well-understood evolutionary events that initiate the Y-chromosome's degeneration will actually fuel its range expansion

Statins in Candidemia: clinical outcomes from a matched cohort study

<p>Abstract</p> <p>Background</p> <p>HMG CoA reductase inhibitors (statins) in patients with bacteremic sepsis have shown significant survival benefits in several studies. There is no data on the effect of statins in candidemic patients, however in-vitro models suggest that statins interfere with ergesterol formation in the wall of yeasts.</p> <p>Methods</p> <p>This retrospective matched- cohort study from 1/2003 to 12/2006 evaluated the effects of statins on patients with candidemia within intensive care units. Statin-users had candidemia as a cause of their systemic inflammatory response and were on statins throughout their antifungal therapy, while non-statin users were matched based on age +/- 5 years and co-morbid factors. Primary analysis was 30-day survival or discharge using bivariable comparisons. Multivariable comparisons were completed using conditional logistic regression. All variables with a p-value less than 0.10 in the bivariable comparisons were considered for inclusion in the conditional logistic model.</p> <p>Results</p> <p>There were 15 statin-users and 30 non-statin users that met inclusion criteria, all with similar demographics and co-morbid conditions except the statin group had more coronary artery disease (P < 0.01) and peripheral vascular disease (P = 0.03) and lower median APCAHE II scores (14.6 vs 17, p = 0.03). There were no differences in duration of candidemia, antifungal therapy or <it>Candida </it>species between the groups. Statins were associated with lower mortality on bivariable (OR 0.09, 95% CI 0.11-0.75, p = 0.03) and multivariable (OR 0.22, 95% CI 0.02-2.4, p = 0.21) analyses compared to controls; although, in the latter the protective effect lacked statistical signficance.</p> <p>Conclusion</p> <p>In our small, single-center matched-cohort study, statins may provide a survival benefit in candidemia, however further studies are warranted to validate and further explore this association.</p

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: A review based on controversial evidence

PURPOSE: A review of the role of the carotenoids, lutein and zeaxanthin, and their function in altering the pathogenesis of age-related macular degeneration (AMD). METHODS: Medline and Embase search. RESULTS: Recent evidence introduces the possibility that lutein and zeaxanthin, carotenoids found in a variety of fruits and vegetables may protect against the common eye disease of macular degeneration. This potential and the lack to slow the progression of macular degeneration, has fueled high public interest in the health benefits of these carotenoids and prompted their inclusion in various supplements. The body of evidence supporting a role in this disease ranges from basic studies in experimental animals to various other clinical and epidemiological studies. Whilst some epidemiological studies suggest a beneficial role for carotenoids in the prevention of AMD, others are found to be unrelated to it. Results of some clinical studies indicate that the risk for AMD is reduced when levels of the carotenoids are elevated in the serum or diet, but this correlation is not observed in other studies. Published data concerning the toxicity of the carotenoids or the optimum dosage of these supplements is lacking. CONCLUSION: An intake of dietary supplied nutrients rich in the carotenoids, lutein and zeaxanthin, appears to be beneficial in protecting retinal tissues, but this is not proven. Until scientifically sound knowledge is available we recommend for patients judged to be at risk for AMD to: alter their diet to more dark green leafy vegetables, wear UV protective lenses and a hat when outdoors. Future investigations on the role of nutrition, light exposure, genetics, and combinations of photodynamic therapy with intravitreal steroid (triamcinolone-acetonide) injections hold potential for future treatment possibilities

The effect of forearm posture on wrist flexion in computer workers with chronic upper extremity musculoskeletal disorders

<p>Abstract</p> <p>Background</p> <p>Occupational computer use has been associated with upper extremity musculoskeletal disorders (UEMSDs), but the etiology and pathophysiology of some of these disorders are poorly understood. Various theories attribute the symptoms to biomechanical and/or psychosocial stressors. The results of several clinical studies suggest that elevated antagonist muscle tension may be a biomechanical stress factor. Affected computer users often exhibit limited wrist range of motion, particularly wrist flexion, which has been attributed to increased extensor muscle tension, rather than to pain symptoms. Recreational or domestic activities requiring extremes of wrist flexion may produce injurious stress on the wrist joint and muscles, the symptoms of which are then exacerbated by computer use. As these activities may involve a variety of forearm postures, we examined whether changes in forearm posture have an effect on pain reports during wrist flexion, or whether pain would have a limiting effect on flexion angle.</p> <p>Methods</p> <p>We measured maximum active wrist flexion using a goniometer with the forearm supported in the prone, neutral, and supine postures. Data was obtained from 5 subjects with UEMSDs attributed to computer use and from 13 control subjects.</p> <p>Results</p> <p>The UEMSD group exhibited significantly restricted wrist flexion compared to the control group in both wrists at all forearm postures with the exception of the non-dominant wrist with the forearm prone. In both groups, maximum active wrist flexion decreased at the supine forearm posture compared to the prone posture. No UEMSD subjects reported an increase in pain symptoms during testing.</p> <p>Conclusion</p> <p>The UEMSD group exhibited reduced wrist flexion compared to controls that did not appear to be pain related. A supine forearm posture reduced wrist flexion in both groups, but the reduction was approximately 100% greater in the UEMSD group. The effect of a supine forearm posture on wrist flexion is consistent with known biomechanical changes in the distal extensor carpi ulnaris tendon that occur with forearm supination. We infer from these results that wrist extensor muscle passive tension may be elevated in UEMSD subjects compared to controls, particularly in the extensor carpi ulnaris muscle. Measuring wrist flexion at the supine forearm posture may highlight flexion restrictions that are not otherwise apparent.</p

Laminin γ2 fragments are increased in the circulation of patients with early phase acute lung injury

Katayama, M., Ishizaka, A., Sakamoto, M. et al. Intensive Care Med (2010) 36: 479. https://doi.org/10.1007/s00134-009-1719-

Feeding behavior of the ctenophore Thalassocalyce inconstans : revision of anatomy of the order Thalassocalycida

© 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Marine Biology 156 (2009): 1049-1056, doi:10.1007/s00227-009-1149-6.Behavioral observations using a remotely operated vehicle (ROV) in the Gulf of California in March, 2003, provided insights into the vertical distribution, feeding and anatomy of the rare and delicate ctenophore Thalassocalyce inconstans. Additional archived ROV video records from the Monterey Bay Aquarium Research Institute of 288 sightings of T. inconstans and 2,437 individual observations of euphausiids in the Gulf of California and Monterey Canyon between 1989 and 2005 were examined to determine ctenophore and euphausiid prey depth distributions with respect to temperature and dissolved oxygen concentration [dO]. In the Gulf of California most ctenophores (96.9%) were above 350 m, the top of the oxygen minimum layer. In Monterey Canyon the ctenophores were more widely distributed throughout the water column, including the hypoxic zone, to depths as great as 3,500 m. Computer-aided behavioral analysis of two video records of the capture of euphausiids by T. inconstans showed that the ctenophore contracted its bell almost instantly (0.5 s), transforming its flattened, hemispherical resting shape into a closed bi-lobed globe in which seawater and prey were engulfed. Euphausiids entrapped within the globe displayed a previously undescribed escape response for krill (‘probing behavior’), in which they hovered and gently probed the inner surfaces of the globe with antennae without stimulating further contraction by the ctenophore. Such rapid bell contraction could be effected only by a peripheral sphincter muscle even though the presence of circumferential ring musculature was unknown for the Phylum Ctenophora. Thereafter, several live T. inconstans were collected by hand off Barbados and microscopic observations confirmed that assumption.Supported by the David and Lucile Packard Foundation and NOAA Grant #NA06OAR4600091

Long-term care cost drivers and expenditure projection to 2036 in Hong Kong

<p>Abstract</p> <p>Background</p> <p>Hong Kong's rapidly ageing population, characterised by one of the longest life expectancies and the lowest fertility rate in the world, is likely to drive long-term care (LTC) expenditure higher. This study aims to identify key cost drivers and derive quantitative estimates of Hong Kong's LTC expenditure to 2036.</p> <p>Methods</p> <p>We parameterised a macro actuarial simulation with data from official demographic projections, Thematic Household Survey 2004, Hong Kong's Domestic Health Accounts and other routine data from relevant government departments, Hospital Authority and other LTC service providers. Base case results were tested against a wide range of sensitivity assumptions.</p> <p>Results</p> <p>Total projected LTC expenditure as a proportion of GDP reflected secular trends in the elderly dependency ratio, showing a shallow dip between 2004 and 2011, but thereafter yielding a monotonic rise to reach 3.0% by 2036. Demographic changes would have a larger impact than changes in unit costs on overall spending. Different sensitivity scenarios resulted in a wide range of spending estimates from 2.2% to 4.9% of GDP. The availability of informal care and the setting of formal care as well as associated unit costs were important drivers of expenditure.</p> <p>Conclusion</p> <p>The "demographic window" between the present and 2011 is critical in developing policies to cope with the anticipated burgeoning LTC burden, in concert with the related issues of health care financing and retirement planning.</p

Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems

Acute gastrointestinal (GI) dysfunction and failure have been increasingly recognized in critically ill patients. The variety of definitions proposed in the past has led to confusion and difficulty in comparing one study to another. An international working group convened to standardize the definitions for acute GI failure and GI symptoms and to review the therapeutic options